Cistanche tuaj yeem tiv thaiv raum Ischemia-reperfusion Injury

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Jan H. Lindeman1, Leonie G. Wijermars1, Sarantos Kostidis2, Oleg A. Mayboroda2, Amy C. Harms3, & et al.

Delayed graft muaj nuj nqi yog qhovmanifestation ntawm ischemia reperfusion raug mobnyob rau hauv cov ntsiab lus ntawm lub raum transplantation. Thaum ntau pua kev cuam tshuamntse txo ischemia reperfusion raug mobHauv cov qauv kev sim, txhua qhov kev kho mob tau ua tsis tiav. Qhov kev soj ntsuam soj ntsuam kev soj ntsuam no tau tshuaj xyuas qhov tshwm sim ntawm metabolic keeb kwm ntawm kev kho mob ischemia reperfusion raug mob sib txuas cov ntaub ntawv los ntawm 18 pre thiab post-reperfusion cov ntaub so ntswg biopsies nrog 36 sequential arteriovenous ntshav samplings tshaj graft nyob rau hauv peb pawg kev tshawb fawb. Cov pab pawg no suav nrog cov neeg nyob thiab cov neeg tuag grafts nrog thiab tsis muaj kev ncua sij hawm graft. Kev faib pab pawg tau ua raws li cov txiaj ntsig kho mob. Lub kaum ntse ntse NMR tau siv rau kev tsom xam cov ntaub so ntswg thiab cov txheej txheem loj spectrometry-based platforms tau siv rau kev tsom xam ntshav ntshav. Tag nrholub raumtau ua haujlwm rau ib xyoos. Kev koom ua ke ntawm cov ntaub ntawv metabolomic tau txheeb xyuas qhov kev ntxub ntxaug kom paub txog kev ua haujlwm qeeb tom ntej. Qhov profile no tau tshwm sim los ntawm post-reperfusion ATP / GTP catabolism (tseem ceeb tsis zoo phosphocreatine rov qab thiab tseem ceeb tsis tu ncua (hypo) xanthine ntau lawm) thiab tseem ceeb cov ntaub so ntswg puas. Kev ua tsis tiav high-zog phosphate rov qab tshwm sim txawm tias qhib glycolysis, fatty acid oxidation, glutaminolysis, thiab autophagia, thiab muaj feem xyuam rau qhov tsis xws luag ntawm qib ntawm oxoglutarate dehydrogenase complex hauv Krebs lub voj voog. Kev kho mob qeeb graft muaj nuj nqi vim ischemia reperfusion raug mob cuam tshuam nrog post-reperfusion metabolic vau. Yog li, kev siv zog ua kom qeeb qeeb kev ua haujlwm vim yog kev raug mob ischemia reperfusion yuav tsum tsom rau kev txuag cov metabolism hauv lub cev, los ntawm kev khaws cia kev ncaj ncees ntawm Krebs lub voj voog thiab / lossis los ntawm kev nrhiav cov txheej txheem metabolic. Raum International (2020) 98, 1476–1488; https://doi.org/10.1016/j.kint.2020.07.026

KEYWORDS: ATP; ncua graft muaj nuj nqi; glycolysis; ischemia reperfusion raug mob; metabolism; oxidative phosphorylation

cistanche teebmeem: tiv thaivischemia-reperfusion raug mob

ischemia reperfusion raug mob (IRI)yog qhov tshwm sim ntawm cov ntaub so ntswg puas tsuaj tom qab reperfusion ntawm yav tas los ischemic cov ntaub so ntswg.1,2 Nws yog lub ntsiab contributor rau lub cev puas tsuaj tom qab myocardial los yog hlwb infarction3 thiab graft puas tom qab transplantation.4 Txawm hais tias myriad interventions quench IRI nyob rau hauv preclinical qauv, soj ntsuam kev vam meej tseem nyob. kom ua tiav.3,4 Yog li, muaj qhov sib txawv ntawm kev txhais lus ntawm preclinical qauv thiab cov ntsiab lus kho mob.

Delayed graft function (DGF) yog qhov tshwm sim ntawm IRI nyob rau hauv qhov chaw ntawmraumtransplantation.5 DGF yog txhais raws li qhov xav tau rau kev lim ntshav hauv thawj lub lim tiam lossis lub lis piam tom qab hloov pauv.6 Txawm hais tias DGF tsis tshua muaj tshwm sim nyob rau hauv cov ntsiab lus ntawm cov txheej txheem nyob-pab pub graft, nws cuam tshuam txog li 90 feem pua ​​​​ntawm cov neeg tuag pub dawb graft transplantations.6 Previous Kev ua haujlwm tau pom muaj kev sib koom ua ke ntawm qhov xwm txheej DGF thiab post-reperfusion normoxic glycolysis.7 Qhov kev soj ntsuam no txhais tau hais tias DGF cuam tshuam rau qhov tsis xws luag hauv graft lub zog homeostasis vim qhov tshwm sim ntawm mitochondrial dysfunction nyob rau hauv lub reperfusion theem.7 ntawm lub hauv paus no, peb xav tias kev kho mob DGF cuam tshuam nrog thiab tej zaum yuav raug tsav los ntawm metabolic defect (los yog tsis xws luag). Lub hom phiaj ntawm txoj kev tshawb no yog los ua qhov kev soj ntsuam tob tob ntawm cov lus teb metabolic rauischemia-reperfusionnrog thiab tsis muaj IRI (DGF). Qhov kev tshuaj ntsuam xyuas metabolic no yog ua raws li kev sib koom ua ke, lub sijhawm daws teeb meem uas koom nrog kev soj ntsuam raws li kev soj ntsuam ntawm arteriovenous concentration (AV) qhov sib txawv ntawm reperfused grafts thiab parallel profifiling ntawm graft (cov ntaub so ntswg) biopsies. Peb pawg kawm tau suav nrog: grafts los ntawm tus neeg pub dawb grafts nrog thiab tsis muaj tom qab IRI thiab cov neeg pub dawb nyob. Kev faib pab pawg ntawm cov neeg pub dawb tuag (þDGF thiab -DGF, feem) tau ua rov qab los ntawm lawv cov txiaj ntsig kho mob. Cov neeg pub nyiaj nyob hauv lub neej tau suav nrog kev siv vim tias cov grafts no cuam tshuam nrog kev ua haujlwm sai sai tom qab rov ua dua. Txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau txhawm Cov ntaub ntawv raug nthuav tawm raws li.

(Sau ntawv: Jan H. Lindeman, Department of Surgery, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands. E-mail: Lindeman@lumc.nl Tau txais 20 Lub Ib Hlis 2020; hloov kho 8 Lub Rau Hli 2020; txais 2 Lub Xya Hli 2020; luam tawm online 8 Lub Yim Hli 2020)

cistanche teebmeem: tiv thaivischemia-reperfusion raug mob

TSEEM CEEB

Cov qauv kev tshawb fawb suav nrog 53 tus neeg mob. Paired cov ntaub so ntswg biopsies tau txais los ntawm 18 tus neeg mob, thiab cov qauv AV ua ntu zus tau ua hauv 36 tus neeg mob. Ib tus neeg mob tau txais ob qho tib si biopsies thiab tau kuaj AV. Cov ntaub ntawv kho mob rau 3 pawg kawm tau pom nyob rau hauv Table Ntxiv S1A (cov ntaub so ntswg biopsies) thiab S1B (AV sampling). Tag nrho cov teeb meem DGF xav tau ntau qhov kev lim dej hauv ib lub sijhawm ntawm tsawg kawg 7 hnub, thiab txhua qhov pom tau tias muaj kev ua haujlwm zoo. Tsis muaj ib tus neeg tuag pub dawb uas tsis muaj DGF yuav tsum tau lim ntshav tom qab hloov pauv. Ib xyoos graft ciaj sia yog 100 feem pua.

Peb thawj zaug tshawb nrhiav qhov sib txawv ntawm cov npe metabolic rau 3 pab pawg neeg pub dawb (qhov muaj sia nyob [saib] tus neeg pub khoom noj khoom haus, -DGF cov neeg pub dawb tuag, thiab þDGF [IRI] cov neeg pub dawb tuag) los ntawm kev kos cov plasma metabolome (AV sib txawv) rau { {1}}minutes post-reperfusion time point (Daim duab 1a) thiab covcov ntaub so ntswg metabolome(cov ntaub so ntswg biopsies) rau 40-feeb tom qab-reperfusion lub sij hawm taw tes (Daim duab 1b). Cov ntsiab lus ntawm lub sij hawm no tau raug xaiv kom tsis txhob cuam tshuam los ntawm kev ntxuav tawm ntawm cov metabolites uas tau khaws cia thaum lub sij hawm ischemia lossis txias cia, los yog cov khoom siv ntawm cov kua dej khaws cia (xws li, histidine washout los ntawm cov neeg pub khoom noj khoom haus nyob; Cov duab ntxiv S1 qhia txog kev xaiv siv H [Histidine] TK preservation kua nyob rau hauv cov grafts).7 Cov txiaj ntsig (z-cov qhab nia) rau lub sijhawm cov ntsiab lus no tau muab sau tseg rau hauv daim ntawv qhia tshav kub hauv daim duab 1a (AV sib txawv) thiab 1b (cov ntaub so ntswg). Kev pab pawg ntawm cov ntaub ntawv tau ua raws li 6 pawg uas npog tag nrho cov ntaub ntawv metabolic: (i) nucleoside triphosphate catabolism, (ii) b-oxidation, (iii) glycolysis/glutaminolysis, (iv) autophagy, (v) Krebs cycle defects, thiab (vi) cell puas.

Daim ntawv qhia tshav kub rau AV qhov sib txawv qhia qhov sib npaug ntawm cov kab mob metabolic rau cov neeg muaj sia nyob thiab -DGF grafts thiab kos npe kom meej meej rau þDGF grafts (Daim duab 1a). Ib qho zoo sib xws, txawm hais tias tsawg dua, tus qauv tau pom zoo rau cov ntaub so ntswg metabolites (Daim duab 1b). Daim ntawv qhia tshwj xeeb ntawm -DGF thiab þDGF grafts (tsis muaj cov neeg pub dawb nyob) ua rau cov lus xaus zoo sib xws (tsis pom), qhia tias kev suav nrog cov neeg pub dawb nyob (xws li) cov ntaub ntawv hauv kev tshuaj xyuas tsis cuam tshuam nrog cov lus xaus ntawm kev tshuaj xyuas. Ua ke, cov ntaub ntawv muab tag nrho cov metabolic kos npe rau lub raum IRI.

Txhawm rau kom pom tseeb, cov ntaub ntawv ntawm tus kheej metabolites tau nthuav tawm nyob rau hauv cov nqe lus ntawm 6 pawg metabolic. Txhawm rau kom tsis txhob cuam tshuam los ntawm thawj zaug ntxuav tawm ntawm cov metabolites uas tau khaws cia thaum lub caij txias txias hauv thawj feeb ntawm kev rov ua dua, kev kwv yees rau kev tso tawm tom qab tso tawm los yog uptake yog raws li kev sib koom ua ke ntawm AV sib txawv rau 10- rau {{3 }}feeb tom qab-reperfusion lub sijhawm ncua sijhawm (chaw nruab nrab ntawm cov nkhaus).

Qhov thib ib pawg ntawm metabolites ("nucleoside triphosphate catabolism") qhia txog qhov ua rautsis tu ncua post-reperfusionmetabolic incompetence ("lub hwj chim kaw") nyob rau hauv grafts nrog tom qab DGF (þDGF). Qhov kev txiav txim siab no yog ua raws li qhov tsis zoo tom qab rov qab rov qab los ntawm lub zog siab phosphate-buffer phosphocreatine hauv þDGF grafts (P < 0.001;="" daim="" duab="" 2a),="" thiab="" los="" ntawm="" kev="" xa="" mus="" tas="" li="" -reperfusion="" adenosine="" triphosphate="" guanosine="" triphosphate="" (atp="" gtp)="" catabolism.="" cov="" tom="" kawg="" yog="" rov="" qab="" nyob="" rau="" hauv="" qhov="" kev="" tso="" tawm="" txuas="" ntxiv="" (av="" sib="" txawv)="" ntawm="" hypoxanthine="" thiab="" xanthine="" (daim="" duab="" 2b="" thiab="" c,="" p="">< 0.0001="" thiab="" 0.02,="" raws="" li),="" cov="" khoom="" degradation="" ntawm="" atp="" thiab="" gtp="" los="" ntawm="" cov="" grafts.="" cov="" ntaub="" ntawv="" rau="" cov="" ntaub="" so="" ntswg="" pre-reperfusion="" biopsies="" pom="" cov="" qib="" ntawm="" inosine="" thiab="" hypoxanthine="" tsub="" zuj="" zuj="" ntawm="" qhov="" kawg="" ntawm="" ischemic="" cia="" lub="" sij="" hawm,="" nrog="" rau="" cov="" ntsiab="" lus="" qis="" tshaj="" nyob="" rau="" hauv="" kev="" ua="" neej="" nyob="" thiab="" siab="" tshaj="" nyob="" rau="" hauv="" tuag="" pub="" grafts="" (daim="" duab="" 2d="" thiab="" e).="" post-reperfusion="" (t="" ¼="" 40="" min)="" cov="" ntaub="" so="" ntswg="" hypoxanthine="" thiab="" inosine="" tau="" zoo="" sib="" xws="" thiab="" qis="" hauv="" 3="" pawg="" neeg="" pub="" dawb="" (daim="" duab="" 2d="" thiab="">

Post-reperfusion ATP catabolism nyob rau hauv þDGF grafts tau tshwm sim txawm hais tias muaj qhov pom tseeb tom qab rov ua dua rov qab los ntawm fatty acid b-oxidation (Cov duab ntxiv S2), activated glycolysis / glutaminolysis (Daim duab 3), thiab autophagy (Daim duab 4). Tag nrho 3 hom graft tau pom zoo ib yam ntawm cov ntaub so ntswg b-hydroxybutyrate cov ntsiab lus (Ntxiv daim duab S2A) thiab xaiv clearance (uptake) ntawm nruab nrab-chain fatty acids (C8-C12) los ntawm kev ncig (Ntxiv cov duab S1 thiab S2B-E), qhia tias uniform. rov ua dua ntawm b-oxidation. Txawm li cas los xij, cov ntaub so ntswg sib xyaw ntawm acetyl-carnitine hauv -DGF thiab þDGF tuag pub dawb grafts (Cov duab ntxiv S2F), thiab ntxuav tawm (AV sib txawv) ntawm acetylcarnitine los ntawm þDGF grafts (Cov duab ntxiv S2G, P < 0.03)="" graded="" defects="" nyob="" rau="" hauv="" pov="" tseg="" ntawm="" acetyl="" pawg="" tsim="" thaum="" lub="" sij="">

Cistanche tshuaj ntsuab

Daim duab qhia ntawm glycolysis/glutaminolysis tes hauj lwm (Daim duab 3) tau pom cov qib qabzib sib npaug ntawm cov nqaij mos (Daim duab 4a) thiab tau lees paub qhov tsis tu ncua tom qab reperfusion normoxic glycolysis raws li ib qho tshwj xeeb ntawm þDGF pub grafts (viz. pheej lactate thiab pyruvate 3 tso tawm (Daim duab,<0.0001 and=""><0.04, respectively)="" and="" release="" of="" the="" transamination="" products="" alanine="" and="" aspartate="" (figure="" 3e="" and="" f,="" p="" <="" 0.02="" and="" <="" 0.0001,="" respectively).="" serine="" (figure="" 4b)="" and="" phosphoserine="" (supplementary="" figure="" 3d)="" released="" from="" þdgf="" grafts="" may="" (partially)="" reflflect="" transamination="" of="" the="" glycolysis="" intermediate="" phosphoglycerate.="" persistent="" post-reperfusion="" glutamate="" release="" (figure="" 3k,="" p="" <="" 0.002),="" selective="" release="" of="" the="" transamination="" products="" alanine="" and="" aspartate="" (figure="" 3e="" and="" f),="" and="" exhaustion="" of="" the="" tissue="" asparagine="" pool="" (figure="" 3j,="" p="" <="" 0.03)="" in="" þdgf="" grafts="" imply="" continued="" post-reperfusion="" glutaminolysis="" (alanine)="" and="" glutamine="" shuttling="" (asparagine="" aspartate)8="" in="" the="" post-reperfusion="" phase="" of="" these="" grafts.="" moreover,="" the="" exclusive="" release="" of="" serine,="" methionine,="" and="" tyrosine="" (figure="" 4a–c,="" all="" ps="" <="" 0.0005),="" along="" with="" disposal="" of="" butyryl="" carnitine="" and="" isovaleryl="" carnitine="" (figure="" 4d="" and="" e,="" p=""><0.006 and=""><0.003, respectively),="" deamination="" products="" of="" the="" branched-chain="" amino="" acids9,10="" from="" þdgf="" grafts,="" but="" not="" from="" the="" other="" graft="" types="" (figure="" 4a–e),="" implies="">post-reperfusionautophagy hauv cov grafts.11.

Daim duab 1|Clustered heat maps rau arterial-venous metabolite concentration sib txawv ntawm tus pub graft ntawm 30 feeb thiab cov ntaub so ntswg metabolite ntsiab lus 40 feeb tom qab reperfusion. (a) Clustered tshav kub daim ntawv qhia rau arterial-venous metabolite concentrations ntawm t ¼ 30 feeb tom qab reperfusion. Cov kab sawv cev rau 3 pab pawg neeg pub dawb (nyob pub dawb grafts [ pab pawg neeg siv, n ¼ 10]; tuag pub grafts yam tsis tau ncua sij hawm grafts [DGF {–DGF, n ¼ 10}], thiab tuag pub dawb grafts nrog tom qab DGF [þDGF, n° 16]). Cov tshuaj sib xyaw ua ke raws li 5 pawg metabolic thiab, nyob rau hauv txhua pawg, suav nrog cov qhab-nees z ntawm cov neeg pub dawb nyob. Ntsuab reflects net uptake los ntawm graft thiab liab reflects lub net tso tawm los ntawm graft. (Txuas ntxiv)

Daim duab 1 (Txuas ntxiv) (b) Clustered tshav kub daim ntawv qhia rau cov ntaub so ntswg metabolites pom nyob rau hauv HR khawv koob lub kaum ntse ntse nuclear sib nqus resonance tsom xam ntawm graft biopsies noj 40 feeb tom qab reperfusion. Cov kab sawv cev rau 3 pab pawg neeg pub dawb (cov neeg pub dawb nyob [paub pab pawg, n ¼ 6, cov neeg pub dawb tuag tsis muaj tom qab DGF [–DGF, n ¼ 6], thiab cov neeg pub dawb tuag nrog tom qab DGF [þDGF, n ¼ 6]). Liab reflects cov ntaub so ntswg cov ntsiab lus saum toj no thiab greenreflects ib cov ntaub so ntswg hauv qab lub geometric txhais tau tias ntawm 3 pawg.

Post-reperfusion acetyl-carnitine accumululation (cov ntaub so ntswg) hauv -DGF thiab þDGF grafts (Daim duab 2f) thiab pib (nyob pub thiab -DGF grafts) thiab txuas ntxiv (þDGF grafts) acetylcarnitine tso tawm (P < 0="" 0.="" }}3)="" qhia="" txog="" ib="" ntus="" (–dgf="" grafts)="" lossis="" tsis="" tu="" ncua="" (þdgf="" grafts)="" impaired="" acetyl-coenzyme="" a="" pov="" tseg="" tom="" qab="" rov="" ua="" dua="" (cov="" duab="" ntxiv="" 2g).="" txawm="" hais="" tias="" qhov="" sib="" xyaw="" no="" tuaj="" yeem="" tshwm="" sim="" los="" ntawm="" exaggerated="" glycolysis="" thiab="" b-oxidation,="" nws="" kuj="" tseem="" yuav="" qhia="" tau="" tias="" tsis="" muaj="" acetyl="" pov="" tseg="" vim="" krebs="" lub="" voj="" voog="" tsis="" zoo.="" rau="" þdgf="" grafts,="" cov="" txheej="" txheem="" tom="" kawg="" yog="" txhawb="" los="" ntawm="" kev="" xaiv="" thiab="" tsis="" tu="" ncua="" tso="" tawm="" ntawm="" krebs="" lub="" voj="" voog="" nruab="" nrab="" a-ketoglutarate="" (daim="" duab="" 5c,="" p="">< 0.0005)="" ua="" ib="" qho="" tshwj="" xeeb="" hauv="" cov="" grafts="" thiab="" los="" ntawm="" kev="" tsis="" zoo="" ntawm="" cov="" ntaub="" so="" ntswg="" succinate="" hauv="" þdgf="" grafts.="" (daim="" duab="">

Ib pawg kawg ntawm kev ntxub ntxaug metabolites cuam tshuam rau kev puas tsuaj ntawm tes tsis tu ncua. Cov pawg no suav nrog covpost-reperfusiontso tawm ntawm uracil, ib qho cim cim ntawm kev puas tsuaj ntawm tes12,13 (Cov duab ntxiv S3A, P < 0.0001)="" thiab="" cov="" amino="" acid="" derivates="" uas="" koom="" nrog="" lub="" hydrolysis="" ntawm="" plasmalogens="" (viz.="" phospho-ethanolamine,="" ethanolamine,="" thiab="" phospho-serine;="" supplementary="" figure="" s3bd,="" p="">< 0="" 001;="" cov="" duab="" ntxiv="" s1).="" txawm="" hais="" tias="" tsis="" muaj="" qhov="" sib="" txawv="" ntawm="" av="" rau="" choline="" hauv="" pawg="" þdgf="" (p="" ¼="" 0.60),="" qhov="" kev="" soj="" ntsuam="" no="" yog="" qhov="" sib="" txawv="" ntawm="" cov="" choline="" uptake="" hauv="" cov="" neeg="" pub="" nyob="" thiab="" -dgf="" pawg="" (p=""><0.0001 thiab="" 0.02,="" raws="" li).="" li="" no,="" hauv="" þdgf="" grafts,="" hydrolysis="" ntawm="" choline="" plasmalogens="" yuav="" npog="" los="" ntawm="" choline="" uptake.="" xws="" li="" ib="" tug="" mechanism="" yog="" txhawb="" los="" ntawm="" kev="" xaiv="" thiab="" nce="" qib="" ntawm="" betaine,="" cov="" khoom="" oxidation="" ntawm="" choline14="" nyob="" rau="" hauv="" þdgf="" pawg="" (cov="" duab="" ntxiv="" s3g,="" p=""><>

Cov kev soj ntsuam yav dhau los koom nrog qhov xwm txheej IRI nrog kev pheej hmoopost-reperfusionATP catabolism thiab kev puas tsuaj ntawm tes tsis tu ncua nyob rau hauv cov ntsiab lus ntawm mitochondrial tsis ua haujlwm thiab ua kom cov glycolytic thiab lipolytic txoj hauv kev (Daim duab 6). Xav txog lub luag haujlwm tseem ceeb ntawm ATP hauv cellular homeostasis thiab ciaj sia taus, nws tau xav tias kev nrhiav neeg ua haujlwm ntawm ATP-regenerative pathways (viz. ywj siab ntawm mitochondrial respiration) yuav muaj txiaj ntsig. Hauv cov ntsiab lus no, peb suav tias yog inosine, ib qho nucleoside uas tuaj yeem tsim ATP los ntawm txoj hauv kev tsis zoo. Raws li pom nyob rau hauv daim duab 7, tsis muaj kev tiv thaiv los yog cawm inosine tus me nyuam (nyob rau hauv ntau txog 10 mMol / l) cawm ATP kev qaug zog tom qab chemically induced metabolic tuag tes tuag taw.

Daim duab 3|Tom qab reperfusion glycolysis thiab glutaminolysis. Curves rau arterial venous sib txawv (liab nkhaus yog arterial, lub xiav nkhaus yog venous). Cov ntaub so ntswg biopsies (bar graphs): cov kab dawb sawv cev ua ntej reperfusion biopsies; grey bars sawv cev tom qab reperfusion biopsies (t ¼ 40 min tom qab reperfusion). * P <0.05. (a)="" cov="" ntaub="" so="" ntswg="" muaj="" piam="" thaj.="" (b-i)="" glycolysis="" intermediates:="" lactate,="" pyruvate,="" alanine,="" aspartate,="" thiab="" asparagine.="" (k,="" li).="" glutaminolysis="" intermediates="" glutamine="" thiab="" glutamate.="" cov="" ntaub="" so="" ntswg="" nuclear="" magnetic="" resonance="" (nmr;="" n="" ¼="" 6="" ib="" pawg):="" (a)="" cov="" ntaub="" so="" ntswg="" rov="" qab="" nyob="" rau="" hauv="" cov="" neeg="" pub="" dawb.="" (d,="" f,="" h)="" ruaj="" khov="" lactate,="" alanine,="" thiab="" aspartate="" cov="" ntaub="" so="" ntswg="" cuam="" tshuam="" txog="" kev="" ntxuav="" tawm="" ntawm="" cov="" intermediates="" (txuas="">

Daim duab 3 (txuas ntxiv) los ntawm lub raum. (j) Unmeasurable ntaub so ntswg asparagine nyob rau hauv þ qeeb graft muaj nuj nqi (DFG) post-reperfusion biopsies. Arterial-venous (AV) concentration txawv (n ¼ 10, 10, thiab 16 hauv cov neeg nyob, –DGF, thiab þDGF pawg, raws li: (b,c) persistent post reperfusion lactate (P < 0="" 0001)="" thiab="" pyruvate="" (p="">< 0.04)="" tso="" tawm="" ntawm="" cov="" grafts.="" (e)="" alanine="" (p="">< 0.02),="" (g)="" aspartic="" acid="" (p="">< 0.0001),="" thiab="" (þk)="" glutamate="" tso="" tawm="" (qeeb="" graft="" muaj="" nuj="" nqi="" (dgf="" grafts="" qhia="" normoxic="" glycolysis="" hauv="" p="">< 0.002)="" los="" ntawm="" þdgf="" grafts="" qhia="" oxidation="" glutamine="" tsis="" tu="" ncua="" tsis="" muaj="" qhov="" sib="" txawv="" ntawm="" av="" tseem="" ceeb="" rau="" glutamine="">

cistanche teebmeem: tiv thaivkab mob raum

Kev sib tham

Los ntawm txoj kev tshawb no, ua nyob rau hauv cov ntsiab lus ntawm kev kho mob raum hloov, daim duab tshwm sim ntawm IRI (DGF) yog ib tug tshwm sim ntawm ib tug yuav luag instantaneous thiab persistent post reperfusion tsis ua hauj lwm ntawm oxidative phosphorylation thiab activated normoxic glycolysis uas tsis muaj peev xwm txhawb nqa lub zog homeostasis. Nyob rau hauv tas li ntawd, lub high-zog phosphate pas dej ua ke yog zuj zus lawm, thiab cellular kev ncaj ncees yuav tsis tau khaws cia, ua rau cov ntaub so ntswg puas.

Qhov kev tshawb fawb soj ntsuam no yog ua raws li kev sib koom ua ke ntawm cov ntaub ntawv metabolic tau muab los ntawm cov ntaub so ntswg biopsies coj tam sim ua ntej thiab 40 feeb tom qab rov ua dua thiab los ntawm kev soj ntsuam sib txuas ntawm AV qhov sib txawv ntawm cov khoom siv rov ua dua tshiab. Cov kev sib txawv AV no tsis yog tsuas yog muab ib qho kev qhia rau lub sijhawm thiab lub sijhawm ntawm metabolic (mal) adaptions tab sis kuj tso cai rau kev coj tus cwj pwm pom nyob rau hauv cov ntaub so ntswg biopsies thiab kev txaus siab ntawm metabolite clearance ntawm (xws li, lactate) los yog uptake los ntawm (xws li, nruab nrab. -chain fatty acids) lub voj voog.15,16 Qhov kev daws teeb meem ntawm AV mus kom ze yog qhia meej meej los ntawm cov ntaub ntawv acylcarnitine, uas tsis tsuas yog qhia kev xaiv uptake ntawm nruab nrab-chain fatty acids tab sis kuj qhia tias unsaturated C14 carnitine hom tetradecenoyl thiab tetradecadienyl carnitine. coj zoo ib yam li cov saw hlau nruab nrab fatty acids (Cov ntaub ntawv ntxiv S1) thiab yuav tsis cia siab rau cov fatty acid transporters.17 Qhov tseeb, nyob rau hauv cov txheej txheem ntawm kev soj ntsuam cov ntaub ntawv, nws tau pom tias ib qho kev cia siab rau cov ntaub so ntswg biopsies yuav tsis pom feem ntau cov lus xaus hauv txoj kev tshawb no. vim tias feem ntau ntawm cov metabolites tsim tau zoo tshem tawm hauv kev ncig. Kev ruaj khov ntawm cov hlab ntsha hauv cov ntshav qhia tau tias cov ntshav homeostasis raug tswj xyuas, thiab yog li ntawd, cov metabolites tso tawm lossis nqus tau zoo pov tseg lossis rov ntxiv rau lwm qhov.15,16 Saib xyuas cov ntaub so ntswg ruaj khov, tab sis qhov tseeb AV qhov sib txawv tawm tsam qhov kev siv tau ntawm cov ntaub so ntswg-raws li metabolomic ntsuam xyuas. Nco ntsoov tias, nyob rau hauv cov ntsiab lus ntawm cov neeg mob lub raum tuag thiab lub sijhawm ntawm txoj kev tshawb no, kev tso zis tsis yog qhov cuam tshuam vim tias tag nrho cov neeg pub dawb tuag tau mob rau lub sijhawm ntsuas 40- feeb.

Daim phiajcim ntawm cov ntaub ntawv txheeb xyuas qhov metabolic hneev taw uas muaj kev ntxub ntxaug rau IRI. Tshwj xeeb, theem reperfusion ntawm grafts nrog rau yav tom ntej DGF yog uniformly thiab txawv txav ntawm oxidative phosphorylation loj heev (histotoxic hypoxia) 18 thiab compensatory normoxic glycolysis uas tsis tuaj yeem txhawb nqa ATP rov tsim dua tshiab. Cov lus xaus kawg yog raws li qhov ua tsis tiav rov qab los ntawm lub zog siab phosphate tsis muaj phosphocreatine19 thiab ntawm qhov tsis tu ncua tom qab rov ua dua ATP / GTP catabolism rov qab los ntawm kev txuas ntxiv (hypo) xanthine tso tawm. Qhov tseeb, kwv yees ntawm adenosine poob rau þDGF grafts raws li kev tso tawm hypoxanthine (AV sib txawv) hauv 30 feeb tom qab reperfusion (kwv yees raws li qhia tom qab reperfusion flflow rates, 20 nruab nrab.cov ntaub so ntswghuab hwm coj, 21 thiab raum ATP cov ntsiab lus22) qhia tias ze rau kev qaug dab peg ATP pas dej 30 feebpost-reperfusion. Kev qaug zog tseem ceeb ntawm lub pas dej ATP tuaj yeem ua rau muaj kev cuam tshuam catabolic uas ua rau lub cell tsis teb rau kev rov tsim kho ntawm cov proton-motive rog uas tsav ATP tiam, ua rau lub cell tsis teb rau cov tswv yim cawm.

Qhov post-reperfusion ATP tsis txaus thiab histotoxic hypoxia hauv þDGF grafts yuav underlie qhov kev xaiv tso tawm ntawm cov amino acids txuam nrog hydrolysis ntawm phospholipids (plasmalogens) hauv þDGF grafts. Cov kev tshawb fawb tshawb fawb pom tias hydrolysis ntawm plasmalogens thiab phospholipids yog ib qho tseem ceeb ntawm cov ntaub so ntswg hypoxia, 23 thiab hydrolysis ntawm plasmalogens tau piav qhia nyob rau hauv cov ntsiab lus ntawm ischemic raum raug mob.24 Mechanistically, qhov tshwm sim no tau txuas mus rau membrane translocation thiab activation ntawm calcium-cytosolic. ywj siab phospholipase A2 uas tshwm sim los ntawm hypoxia-driven complex tsim ntawm phospholipase thiab ib tug phosphofructokinase regulatory keeb. Nco ntsoov tias qhov kev hloov pauv ntawm kev rov qab ua dua tshiab ntawm (phospho-) ethanolamine tso tawm los ntawm cov neeg pub dawb thiab -DGF grafts, nrog rau kev tso tawm tsis tu ncua hauv þDGF grafts, tuaj yeem cuam tshuam cov qib sib txawv thiab cov nqi ntawm metabolic rov qab. Txawm li cas los xij, thaum cov ntaub ntawv dhau los qhia txog lub luag haujlwm ntawm cytosolic calcium-yooj yim phospholipase A2,25,26 tau pom qhov sib txawv ntawm AV rau betaine thiab (phospho-)ethanolamine cuam tshuam rau kev ua kom ntau dua ntawm phospholipases uas kuj muaj hom C-phospholipases (phospho-amine) thiab D-phospholipases (ethanolamine / choline). Ib yam li ntawd, depletion ntawm cov ntaub so ntswg asparagine (Daim duab 4j) thiab tso tawm ntawm aspartate (Daim duab 4g) los ntawm þDGF grafts tuaj yeem cuam tshuam kev ua haujlwm tsis zoo asparagine synthase vim ATP depletion.

Daim duab 4|Ua kom muaj zog tom qab reperfusion autophagia hauv D qeeb graft muaj nuj nqi (DGF) grafts. Curves rau arterial-venous sib txawv (liab nkhaus yog arterial, xiav nkhaus yog venous). Cov ntaub so ntswg biopsies (bar graphs): cov kab dawb sawv cev ua ntej reperfusion biopsies; grey bars sawv cev rau post reperfusion biopsies (t ¼ 40 min tom qab reperfusion). * P <0.05. (a–c)="" post-reperfusion="" tso="" tawm="" ntawm="" methionine,="" serine,="" thiab="" tyrosine="" (txuas="">

Daim duab 5|Post-reperfusion Krebs lub voj voog tsis zoo hauv grafts nrog rau yav tom ntej ncua kev graft muaj nuj nqi (DGF). Curves rau arterial-venous concentration (AV) txawv (liab nkhaus yog arterial, xiav nkhaus yog venous). Cov ntaub so ntswg biopsies (bar graphs): cov kab dawb sawv cev ua ntej reperfusion biopsies; grey bars sawv cev rau post-reperfusion biopsies (t ¼ 40 min tom qab reperfusion). *P < {{10}}.05.="" (a–h)="" av="" sib="" txawv="" rau="" krebs="" cycle="" intermediates="" (n="" ¼="" 10,="" 10,="" thiab="" 16="" hauv="" cov="" neeg="" nyob,="" –dgf,="" thiab="" þdgf="" pawg,="" raws="" li):="" kev="" tso="" tawm="" tsis="" tu="" ncua="" ntawm="" a-ketoglutarate="" (los="" ntawm="" þdgf="" grafts;="" p="">< 0.001)="" .="" (e,="" g)="" cov="" ntaub="" so="" ntswg="" tom="" qab="" reperfusion="" succinate="" rov="" qab="" hauv="" þdgf="" grafts="" (p=""><>

Post-reperfusion ATP catabolism nyob rau hauv þDGF grafts tshwm sim txawm hais tias muaj kev ua haujlwm ntawm catabolic txoj hauv kev: glycolysis, b-oxidation ntawm nruab nrab-chain fatty acids (ib txwm qhib rau txhua hom grafts), glutaminolysis (tseem ua rau lub sijhawm ua haujlwm ntawm reperfusion hauv cov neeg pub dawb thiab -D ), thiab activated autophagy. Qhov tseeb, post-reperfusion tso tawm ntawm isovaleryl- thiab butyryl carnitine, deamination cov khoom ntawm branched-chain amino acids isoleucine thiab leucine, 11 raug txheeb xyuas raws li kev ntxub ntxaug biomarkers rau yav tom ntej DGF.

Kev tso tawm tsis tu ncua ntawm acetylcarnitine thiab pyruvate los ntawm þDGF grafts qhia tau hais tias fluxes tsim los ntawm txoj kev qhib catabolic tshaj lub peev xwm oxidative. Tom qab reperfusion ketoglutarate tso tawm, net uptake ntawm nws precursor lub citrate thiab isocitrate los ntawm kev ncig, thiab ua tsis tiav cov ntaub so ntswg succinate rov qab txhais tau hais tias lub impaired oxidative phosphorylation cuam tshuam nrog rau theem ntawm oxoglutarate dehydrogenase complex. Tshwj xeeb tshaj yog, cov kev soj ntsuam metabolic hneev taw thiab lub sijhawm ntawm kev cuam tshuam metabolic tsis qhia lub luag haujlwm rau kev hloov pauv ntawm Krebs cycle27,28 nyob rau hauv tsis tu ncua metabolic dysregulation, muab cov pov thawj ntxiv uas tau pom tias cov txheej txheem rau IRI hauv nas28 tsis txhais lus rau tib neeg. context.29.

Impaired oxoglutarate dehydrogenase kev ua haujlwm tuaj yeem tshwm sim los ntawm ischemia-txog kev puas tsuaj rau lub complex30 tab sis kuj tseem tuaj yeem koom nrog, lossis ua rau exaggerated los ntawm, kev puas tsuaj.post-reperfusionImpaired oxoglutarate dehydrogenase kev ua haujlwm yuav tshwm sim los ntawm ischemia-txog kev puas tsuaj rau lub complex30 tab sis kuj yuav koom nrog, los yog exaggerated los ntawm, impaired post-reperfusion muaj ntawm nws cov cofactors acetyl-coenzyme A, FADþ, thiab NADþ. 31 Rau þDGF grafts, xws li deficities yuav tshwm sim vim post-reperfusion acetyl-coenzyme A washout thiab ib tug cuam tshuam cellular redox raws li txoj cai (txo kev ntxhov siab nrog impaired NADþ muaj), ib qho kev xav txhawb los ntawm qhov qis lactate-to-pyruvate ratio hauv þDGF grafts. 32.

Qhov no metabolic mus kom ze tsis tso cai rau kev soj ntsuam ntawm kev ua pa ntawm txoj hlab pas. Txawm li cas los xij, yav dhau los peb tau txheeb xyuas qhov cuam tshuam ntawm ischemia reperfusion-txog qhov tsis xws luag hauv ob qho tib si ua pa nyuaj I thiab II.7,29 Raws li cov ntaub ntawv hauv txoj kev tshawb no thiab kev ua haujlwm mitochondrial yav dhau los, ib daim duab tshwm sim ntawm kev kho mob raum IRI yog qhov tshwm sim ntawm thawj (los yog eliciting) insult (s) rau lub mitochondrial Krebs lub voj voog-redox shuttle uas tshwm sim ua ntej los yog nyob rau hauv thawj feeb ntawm reperfusion. Kev ua tsis tiav ntawm cov qib ATP ua rau muaj kev txhawb nqa thiab ua tiav ntawm txoj hauv kev catabolic, uas ua rau muaj kev kub ntxhov ntawm lub zog los ntawm kev ua kom cov cellular NADþ thiab FADþ pas dej ua ke (txo kev ntxhov siab). . Tsis zoo li adenosine, 34 inosine ruaj khov hauv plasma; Nws tau raug txheeb xyuas tias yog lwm qhov chaw ntawm ATP hauv obligatory glycolytic cells (xws li, cov hlwb tsis muaj mitochondria) xws li erythrocytes35 thiab hauv hypoxic lub raum hlwb36 thiab yog sab laug tom qab reperfusion. Hmoov tsis zoo, inosine supplementation tsis tau cawm cellular ATP depletion tom qab raug yuam kom kaw cov metabolic, tawm hauv chav me me rau cov tswv yim cawm metabolic tsom rau quenching IRI, hais txog kev cia siab rau cov tswv yim tiv thaiv kom txwv IRI.

Tonify lub raum cistanche

Muaj kev txwv rau txoj kev tshawb no. Vim muaj ntau qhov kev sib piv, lub peev xwm rau qhov tseem ceeb fifindings vim random lub sij hawm nyob rau hauv qhov chaw ntawm ntau qhov sib piv yog siab. Txawm hais tias peb cov lus xaus tau txais kev txhawb nqa los ntawm kev sib raug zoo lom neeg, cov txiaj ntsig yuav ua rau muaj kev ntxhov siab los ntawm cov teeb meem cuam tshuam nrog ntau qhov kev sib piv.

Ib qho kev txwv ntxiv yog tias txoj kev tshawb fawb yog nyob ntawm cov qauv kuaj mob; Yog li ntawd, clamp freezing yuav tsum tau rau kev ntsuam xyuas ncaj qha ntawm ATP thiab redox xwm txheej tsis tau. Vim tias cov metabolome pom tau meej meej qhov txawv ntawm qhov uas tau tshaj tawm hauv cov qauv tsiaj thiab nws cuam tshuam txog kev ua haujlwm tsis ua haujlwm, peb tsis tuaj yeem ua qhov kev ntsuam xyuas ntxaws ntxiv hauv cov qauv tsiaj lossis ex vivo systems xws li lub cev ua pa. Cov txiaj ntsig hauv qhov kev tshawb fawb no yog rau covraum; yog li ntawd, cov lus xaus rau lwm lub cev tej zaum yuav txawv. Lub hnub nyoog muaj txiaj ntsig zoo tshaj plaws hauv txoj kev tshawb no yog qhov kev xav ntawm cov neeg pub dawb hauv Netherlands. Qhov tseem ceeb, 10- xyoo hloov cov txiaj ntsig rau Netherlands tsawg kawg yog sib npaug rau cov teb chaws uas muaj cov tub ntxhais hluas pub dawb, xws li Tebchaws Meskas.37 Raws li kev cia siab tias feem ntau ntawm þDGF kis yog DCD grafts. Peb pom zoo ib yammetabolic profilerau DBD thiab DCD grafts; Txawm li cas los xij, lub zog ntawm qhov kev tshawb nrhiav no pom tseeb tsawg dhau los txhawm rau txheeb xyuas qhov sib txawv me me ntawm 2 hom pub dawb.

Daim duab 7|Ob qho kev tiv thaiv thiab cawm inosine kev kho mob tsis ua kom rov zoo adenosine triphosphate (ATP) qib. PK-1 lub raum kab ntawm tes tau ruaj khov nrog PercevalHR fluorescent biosensor ntawm ATP-rau-adenosine diphosphate (ADP) piv.

Chemically induced metabolic-paralysis yog induced los ntawm kev ntxiv rotenone/actinomycin/2-deoxyglucose, thiab ATP-rau-ADP piv (kwv yees flfluorescence) tau soj ntsuam. Xim av, tswj; dub, metabolic paralysis tswj; ntsuab, tiv thaiv inosine kev kho mob (10 mMol / l); liab, inosine cawm ntawm t ¼ 15 feeb tom qab induction ntawm metabolic tuag tes tuag taw.

Hauv kev xaus, qhov kev tshawb fawb no qhia tau hais tias kev kho mob raum IRI yog ua ntej los ntawm qhov yuav luag tam sim ntawm metabolic vau thiab nrog rau cov teeb meem muaj zog phosphate. Qhov kev sib sib zog nqus thiab tsis txaus metabolic no thiab nws qhov xwm txheej tam sim no (thiab qhov tshwm sim tsawg kawg ntawm lub sijhawm kho mob) yuav cuam tshuam nrog kev cuam tshuam ntawm cov tshuaj uas nyob ntawm qhov muaj ATP. Qhov no yuav piav qhia txog qhov tsis zoo ntawm kev ua tsis zoo ntawm cov tshuaj preclinical fifindings rau qhov chaw kho mob.2–4 Cov kev soj ntsuam metabolome ntawm kev kho mob DGF sharply contrasts nrog qhia metabolic cov lus teb rau nas, 28 nas, 38 thiab npua, 39,40 uas tag nrho cov qhia txog reinstatement ntawm oxidative phosphorylation nyob rau hauv feeb ntawm reperfusion. Qhov no yuav cuam tshuam txog qhov sib txawv hauv mitochondrial lossis metabolic physiology ntawm cov nas thiab cov tsiaj loj (xws li, ischemia-induced succinate accumululation tsis tshwm sim hauv tib neeg lub raum). rauischemia reperfusionthiab tsuas yog ib pawg ntawm grafts de velops IRI (DGF). Kev faib pab pawg (þDGF lossis -DGF) hauv qhov kev tshawb fawb no tau ua rov qab, thiab yog li nws cais tawm ntawm ischemia reperfusion thiab IRI. Nws tsis tuaj yeem raug cais tawm tias ischemia reperfusion hauv kev sim ua qauv 28,38-40 tsis txaus ua rau IRI.

Txawm hais tias muaj kev puas tsuaj loj heev, tag nrho cov þDGF grafts thaum kawg tau rov qab los, hais txog qhov muaj peev xwm rov qab tau zoo uas tau muab cov kev cuam tshuam txuas (piv txwv li, lim ntshav) muaj. Nco ntsoov, txawm hais tias cov metabolomes zoo sib xws rau DGF hauv grafts muab tau los ntawm cov neeg pub dawb tuag tom qab lub paj hlwb tuag lossis mob plawv ua rau lub cev tsis sib xws, muaj qhov sib txawv ntawm DGF ntawm kev muaj sia nyob mus ntev rau 2 hom pub dawb.41 Qhov tseeb, txawm tias DGF kom meej meej influences ciaj sia taus ntawm grafts los ntawm pub dawb tuag tom qab lub paj hlwb tuag, nws tsis nyob rau hauv xws li grafts los ntawm cardiac donors. Qhov kev sib piv no zoo li xav txog qhov zoo tshaj plaws rov qab muaj peev xwm ntawm grafts los ntawm cov neeg mob plawv tuag.41

Txoj kev

Leiden University Medical Center Pawg Neeg Saib Xyuas Kev Noj Qab Haus Huv tau pom zoo rau txoj cai kawm. Sau ntawv tso cai tau txais los ntawm txhua tus neeg mob. Qhov kev tshawb fawb ib-chaw no suav nrog 53 tus neeg mob uas tau musraumKev hloov pauv: 37 tau ua tiav cov txheej txheem pub dawb pub dawb thiab 16 tus txheej txheem pub dawb. Raws li qhov txiaj ntsig ntawm kev kho mob (DGF), cov neeg tau txais cov nyiaj pub dawb tau muab faib rau pawg þDGF (n ¼ 16) lossis -DGF pawg (n ¼ 10). DGF tau txhais los ntawm qhov xav tau kev lim ntshav hauv thawj lub lim tiam tom qab hloov pauv.6

Txoj kev tshawb no yog ua raws li kev sib koom ua ke ntawm cov ntaub ntawv metabolomics tau los ntawm kev kuaj ntshav ntawm arteriovenous (AV) thaum thawj ib nrab teev ntawm kev rov ua dua, thiab los ntawm cov ntaub so ntswg biopsies tau sau tam sim ua ntej thiab 40 feeb tom qab.

reperfusion.

Sequential AV blood sampling over the graft tau ua nyob rau hauv 36 tus neeg mob (Table Ntxiv S1A). Cov ntshav raum cov hlab ntsha tau sau ntawm 30 s, thiab 3, 5, 10, 20, thiab 30 feeb thiab kuaj ntshav ntawm 0, 10, thiab 30 feeb tom qab rov ua dua.42 Paired pre- thiab post-reperfusion raum. biopsies tau txais tam sim ua ntej thiab 40 feeb tom qab rov ua dua los ntawm 6 nyob thiab 12 tus neeg pub dawb grafts tuag (Sab Ntxiv Table S1B; 1 tus neeg mob muaj ob qho tib si biopsies thiab AV sampled).

Targeted metabolomics tsom xam tau ua los ntawm cov txheej txheem kev khiav hauj lwm uas siv cov txheej txheem loj spectrometry-raws li platforms los yog khawv koob lub kaum ntse ntse nuclear resonance (cov ntaub so ntswg biopsies).43 Metabolites them los ntawm lub platforms tau sau tseg nyob rau hauv Supplementary Table S1.

Lub peev xwm ntawm inosine los cawm cov metabolic deficit thaum lub sij hawm metabolic vau tau sim nyob rau hauv cov kab sib txuas ntawm tubule cell (LLC PK1) ruaj khov nrog PercevalHR flfluorescent ATP adenosine diphosphate biosensor.44.

Hais txog kev txheeb cais, daim ntawv qhia tshav kub tau tsim los ntawm z-cov qhab nia rau txhua tusmetabolite. Nyob rau hauv-pab pawg kev hloov pauv hauv cov ntaub so ntswg metabolite tau sim los ntawm Mann-Whitney test thiab qhov sib txawv ntawm pab pawg los ntawm Wilcoxon test. AV sib txawv tau kwv yees los ntawm kev siv cov qauv sib xyaw ua ke. Kev kho rau ntau qhov kev sim tsis tau ua vim tias txhua qhov kev soj ntsuam yog ib feem ntawm kev sib txuas lus theoretical. Cov ntsiab lus hais txog cov neeg mob thiab cov txheej txheem muaj nyob rau hauv Cov Txheej Txheem Ntxiv.

cistanche extract

Qhia tawm

Txhua tus kws sau ntawv tshaj tawm tsis muaj kev sib tw txaus siab.

TXOJ CAI

Magnetic Resonance core facility yog pab nyiaj los ntawm Kws Kho Mob ntawm NTNU Trondheim, Norway. Txoj kev tshawb no tau nyiaj txiag los ntawm Dutch raum Foundation (Metabolic Salvage Strategies to Improve Transplant Outcome, project17O/11).

SUPPLEMENTARY KHOOM

Cov ntaub ntawv ntxiv (PDF)

Ntxiv cov neeg mob thiab cov txheej txheem.

Tab S1. Tus neeg mob thiab kev hloov pauv cov yam ntxwv ntawm cov txheej txheem uas tau muab cov ntaub so ntswg biopsies tau sau (A) thiab qhov kev kuaj AV tau ua (B).

Tab S2. Platforms thiab lawv cov metabolites yog siv rau cov qauv AV.

Daim duab S1. Tag nrho cov ntaub ntawv metabolic.

Daim duab S2. Rov ua dua ntawm b-oxidation (medium-chain fatty acids) tom qab reperfusion.

Daim duab S3. Xaiv thiab tsis tu ncua tom qab reperfusion ntxuav tawm ntawm uracil thiab phospholipid (plasmalogen)-koom nrog amino acids los ntawm grafts nrog rau yav tom ntej DGF.

Cov ntaub ntawv ntxiv 1. Raw AV cov ntaub ntawv rau acetylcarnitine, organic acids, thiab amino acid platforms.

Cov ntaub ntawv ntxiv 2. Raw AV cov ntaub ntawv rau lub purine thiab pyrimidine platform.

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