Kynurenine Pathway Nyob raum Kab Mob Part 1

Abstrua

Kab mob raumtau dhau los ua ib qho teeb meem kev noj qab haus huv tshaj plaws. Vim muaj coob tus neeg mob laus zuj zus tuaj nrog cov kab mob sib kis, qhov ntau ntawm cov kab mob no yuav nce ntau xyoo tom ntej. Txawm hais tias muaj cov kev kuaj sim, qhov tseeb thiab nrawm ntawm lub raum tsis ua haujlwm tseem tsis tau paub, thiab qhov kev cia siab tsis meej. Ntxiv mus, cov ntaub ntawv ntawm kev kuaj mob thiab prognostic markers nyob rau hauvkab mob raumtsis muaj. Txoj kev kynurenine (KYN) yog ib txoj hauv kev ntawm tryptophan (Trp) degradation, nrog rau cov khoom siv roj ntsha uas nthuav tawm cov khoom tsis meej. Txoj kev KYN paub tias muaj kev vam khom rau kev tiv thaiv kab mob. Raws li covlub raumyog ib qho tseem ceeb hauv nruab nrog cev koom nrog hauv kev tsim, degradation, thiab excretion ntawm Trp kawg cov khoom, pathologies nrog rau lub raum ua rau KYN txoj kev ua ub no cuam tshuam. Qhov kev tshuaj xyuas no yog txhawm rau txheeb xyuas cov kev hloov pauv hauv KYN txoj hauv kev pom nyob rau hauv cov kab mob hauv lub raum feem ntau,mob raum mob (CKD), nrog tshwj xeeb tsom raumob ntshav qab zib raum, mob raum mob (AKI), glomerulonephritis, thiab lub raum graft ua haujlwm saib xyuas. Tsis tas li ntawd, qhov tseem ceeb ntawm KYN txoj kev ua haujlwm hauvraumCov kab mob qog noj ntshav tau tham txog, raws li muaj cov tshuaj pharmacological cuam tshuam rau KYN txoj hauv kev hauv lub raum. Txawm hais tias muaj cov ntaub ntawv kho mob tsawg, KYN txoj hauv kev zoo nkaus li yog lub hom phiaj zoo hauv kev kuaj mob thiab kev kwv yees ntawmkab mob raum.Kev hloov pauv ntawm KYN txoj kev ua haujlwm los ntawm cov kws tshuaj tshuaj yuav tsum tau txiav txim siab hauv kev kho mobkab mob raum.

Ntsiab lus

Tryptophan · Kynurenine · Kynurenic acid ·Mob raum mob · Mob raum raug mob· Hloov raum

Cov ntawv luv

XA Xanthurenic acid

Taw qhia

Kab mob raumsawv cev rau ntau yam kev mob nkeeg, cuam tshuam ntau dua 850 lab tus tib neeg thoob ntiaj teb. Ntawm cov ntaub ntawv tshaj tawm,mob raum mob(CKD) tseem muaj ntau tshajraumkev tsis sib haum xeeb, nrog cov txiaj ntsig tsis zoo. Zuag qhia tag nrho, kab mob plawv yog qhov tseem ceeb ua rau tuag rau cov neeg moblub raum ua haujlwmkev puas tsuaj, thiab yuav tsum muaj qhov tseem ceeb rau kev tiv thaiv zoo thiab kev qhia ntxovraum puasbiomarkers. Oxidative stress, endothelial puas, thiab overactivity ntawm lubrenin-angiotensin system (RAS)thiab adrenergic system yog cov txheej txheem tseem ceeb koom nrog hauv pathogenesis ntawmkab mob raum.Txawm hais tias muaj cov ntaub ntawv tsawg, lub luag haujlwm rau glutamatergic system hauv lub cev thiab cov kab mob pathological hauv lub raum tau raug tshaj tawm.

Txoj kev kynurenine (KYN) yog txoj hauv kev loj ntawm tryptophan (Trp) cov metabolism, ua rau muaj ntau yam tshuaj lom neeg lom neeg (Fig. 1). Kev hloov pauv ntawm Trp los ntawm indoleamine 2,3-dioxygenase (IDO), uas yog nyob ntawm lub cev tiv thaiv kab mob, thiab tryptophan 2,3-dioxygenase (TDO), uas feem ntau qhia hauv daim siab, yog qhov tseem ceeb. kauj ruam hauv KYN txoj kev. TDO tuaj yeem qhib tau los ntawm kev muaj ntau dua substrate, glucocorticoids, txo cov ntaub ntawv ntawm nicotinamide adenine dinucleotide phosphate, thiab kynurenic acid (KYNA). IDO tuaj yeem pom nyob rau hauv feem ntau cov ntaub so ntswg, thiab nyob rau hauv ib txwm muaj mob, nws cov dej num yog tsawg; Txawm li cas los xij, nws cov haujlwm tuaj yeem txhim kho los ntawm proinflammatory

cov neeg ua haujlwm, xws li qog necrosis factor-alpha (TNF-), interleukin (IL) -6, thiab interferon-gamma (IFN- ).

Daim duab 1Kynurenine txoj kev. Tryptophan yog degraded los ntawm IDO los yog TDO rau serotonin los yog N-formylKYN. Tom qab ntawd, cov tsim KYN tuaj yeem raug catabolized rau hauv 3-OHKYN, KYNA, lossis AA. Lub 3-OHKYN tau hloov mus rau XA thiab QA, nrog rau cov khoom kawg NAD. 3-OHKYN 3-hydroxykynurenine, AA anthranilic acid, HAAO 3-hydroxy anthranilic acid dioxygenase, IDO indoleamine 2, 3-dioxygenase, KAT kynurenine aminotransferase, KMO kynurenine 3- monooxygenase (kynurenine 3-}hydroxylase), KYN kynurenine, KYNA kynurenic acid, KZ kynureninase, NAD nicotinamide adenine dinucleotide, N-formylKYN N-formyl kynurenine, QA quinolinic acid, QPRTphohorolinic acid, T-phoricos 2. }}dioxygenase, Trp tryptophan, XA xanthurenic acid. Tsim nrog BioRender.com

Hauv cov kauj ruam tom ntej, KYN yog qhov tshwj xeeb metabolized rau 3-hydroxykynurenine (3-OHKYN) thiab tom qab ntawd mus rau 3-hydroxy anthranilic acid (3-OHAA), quinolinic acid (QA), thiab Thaum kawg nicotinamide adenine dinucleotide (NAD). KYNA yog tsim los ntawm kynurenine aminotransferases (KATs) los ntawm KYN seem. Contrary to feem ntau Trp metabolites, uas muaj cov tshuaj lom, KYNA tau pom tias yog neuroprotective, tshwj xeeb tshaj yog vim yog inhibition ntawm N-methyl-d-aspartate thiab -amino-3-hydroxy-5-methyl{10} }isoxazole propionate acid glutamate receptors, uas kuj tau dav faib rau hauvraum. Ntxiv mus, KYNA yog qhov tsis zoo allosteric modulator ntawm alpha 7-nicotinic receptor thiab agonist ntawm G-protein-coupled receptors nrog rau aryl hydrocarbon receptors (AhRs). Lub luag haujlwm ntawm KYNA hauv kev tswj hwm ntawm lub raum hemodynamics thiab lub plawv dhia hauv cov nas uas muaj ntshav siab tsis ntev los no tau qhia. Vim yog glutamatergic thiab cholinergic neurotransmission modulation, KYN txoj hauv kev tau tshawb pom dav dav hauv cov ntsiab lus ntawm kev puas siab puas ntsws thiab kev puas siab puas ntsws. Txawm li cas los xij, lub luag haujlwm ntawm Trp metabolites nyob rau hauv cov ntaub so ntswg peripheral, tshwj xeeb tshaj yog nyob rau hauv lublub raum,tsis nkag siab zoo. KYN txoj kev metabolite tsub zuj zuj tau pom nyob rau hauv ntau cov ntaub ntawv hais txogmob raum mob (AKI)los yogCKD, thiab cov lus xaus uas tsim nyog thiab meej qhia tias KYN metabolites puas muaj kev cuam tshuam ncaj qha rauraum puasnyuaj kos vimraumfiltration txo qis hauv feem ntau cov kab mob nephrological. Ntxiv mus, cov ntaub ntawv tsim lub luag haujlwm rau KYN txoj hauv kev hauv lub cev tsis muaj zog. Hauv qhov kev tshuaj xyuas no, peb tsom los txheeb xyuas cov kev hloov pauv hauv KYN txoj hauv kev uas tau tshaj tawm hauv cov qauv tsiaj ntawmraumkab mobthiab hauv tib neeg. Tsis tas li ntawd, muaj feem cuam tshuam raukab mob raumKev kho mob tau qhia meej raws li cov kev tshawb fawb luam tawm tsis ntev los no.

Kab mob raum

Ntawm no, peb ua tib zoo tshuaj xyuas qhov kev sib raug zoo ntawm KYN txoj kev ua haujlwm thiab feem ntaumob raum, CKD,nrog kev saib xyuas tshwj xeeb raumob ntshav qab zib raum, AKI, glomerulonephritis, thiab saib xyuaslub raum graft function. Vim muaj coob tus neeg mob qog nqaij hlav hauv lub raum, qhov muaj peev xwm koom tes ntawm KYN txoj hauv kev hauv tus mob no tau tham txog. Thaum kawg, tam sim no kev paub txog tshuaj cuam tshuam rau KYN txoj kev ua haujlwm tau nthuav tawm.

Raws li kev tshawb fawb,cistancheyog ib txwm suav tshuaj ntsuab uas tau siv rau ntau pua xyoo los kho ntau yam kab mob. Nws tau raug pov thawj scientific kom muaj cov tshuaj tiv thaiv kab mob, tiv thaiv kev laus, thiab antioxidant zog. Cov kev tshawb fawb tau pom tias cistanche tau txais txiaj ntsig zoo rau cov neeg mob uas raug kev txom nyem los ntawmkab mob raum.Cov khoom xyaw nquag ntawmCistanchepaub tias txo qhov mob,txhim kholub raum ua haujlwmthiab restore lub raum puas hlwb. Yog li, kev koom ua ke Cistanche nyob rau hauv txoj kev npaj kho mob raum tuaj yeem muab txiaj ntsig zoo rau cov neeg mob hauv kev tswj hwm lawv tus mob.

Nyem rau qhov twg Kuv Yuav Yuav Organic Cistanche Rau Raum Kab Mob

Nug ntau ntxiv: david.deng@wecistanche.com WhatApp:86 13632399501

Cistanchepab txo qis proteinuria, txo qis BUN thiab creatinine qib, thiab txo qis kev pheej hmoo ntxivraum puas.Ntxiv rau,Cistanchekuj tseem pab txo qis cov roj cholesterol thiab triglyceride uas tuaj yeem ua rau muaj kev phom sij rau cov neeg mob uas muaj kab mob raum.

Cistanche covantioxidant thiab anti-aging zog pab tiv thaiv covlub raumlos ntawm oxidation thiab kev puas tsuaj los ntawm dawb radicals. Qhov no txhim kho lub raum noj qab haus huv thiab txo cov kev pheej hmoo ntawm kev tsim teeb meem. Cistanche kuj tseem pab txhawb lub cev tiv thaiv kab mob, uas yog qhov tseem ceeb hauv kev tawm tsamraumkab mobthiab txhawb lub raum noj qab haus huv.

Los ntawm kev sib txuas cov tshuaj suav tshuaj ntsuab thiab cov tshuaj niaj hnub sab hnub poob, cov neeg txom nyem los ntawmkab mob raumtuaj yeem muaj ntau txoj hauv kev los kho tus mob thiab txhim kho lawv lub neej zoo. Cistanche yuav tsum tau siv los ua ib feem ntawm txoj kev npaj kho mob tab sis tsis yog siv los ua lwm txoj hauv kev kho mob.

Mob raum mob (CKD)

CKD yog ib qho teeb meem kev noj qab haus huv tshaj plaws, cuam tshuam ntau dua 10 feem pua ​​​​ntawm cov pej xeem. Qhov xwm txheej ntawm CKD yog nce ntxiv vim cov neeg laus laus thiab ntau dua ntawm cov kab mob sib kis. Mob ntshav qab zib mellitus yog qhov ua rau ntau tshaj plaws ntawm CKD, ua rauraumkev hloov kho hauv ib nrab ntawm cov neeg mob no. Kev tuag ntawm cov neeg mob CKD tau txais kev lim ntshav yog piv rau cov neeg mob uas muaj qee yam qog nqaij hlav hauv nruab nrog cev thiab tau kwv yees tias yuav nce ntxiv rau xyoo tom ntej. Ntawm cov txheej txheem koom nrog hauv CKD pathogenesis, mob ntev, thiab kev ua haujlwm tsis muaj zog yog qhov tseem ceeb tshwj xeeb. Zuag qhia tag nrho, txo qis excretion ntawm cov khoom pov tseg thiab impaired metabolicraummuaj nuj nqipab txhawb rau inflammatory mob thaum lub sij hawm kawm CKD. Yog li ntawd, txoj kev KYN zoo li ua lub luag haujlwm tseem ceeb hauv CKD. Txawm hais tias ob peb tsab ntawv ceeb toom tau luam tawm ntawm lub ncauj lus no, cov ntawv luam tawm los ntawm Pawlak li al. tau nthuav dav peb txoj kev paub txog KYN txoj hauv kev hloov pauv metabolite hauv CKD.

Hauv qhov kev sim ua qauv ntawmCKDHauv cov nas nephrectomized, kuaj pom cov plasma Trp qis dua, qhov plasma 3-OHKYN, KYNA, xanthurenic acid (XA), anthranilic acid (AA), thiab QA concentrations tau nce siab (Fig. 2). Interestingly, tsub zuj zuj ntawm Trp metabolites tau pom tias yog proportional rauraumua haujlwm poob. Ntxiv mus,raumKAT thiab kynurenine 3-monooxygenase (KMO) kev ua haujlwm hauv lub raum nas tau nce, tab sis cov haujlwm ntawm kynureninase (KZ) thiab 3-hydroxy anthranilic acid dioxygenase (HAAO) tau qis dua hauv lub raum tsis ua haujlwm. Hauv lwm txoj kev tshawb fawb, kev ua kom lub raum siab KMO tau lees paub thiab lub luag haujlwm rau siab KYN thiab 3-OHKYN qib hauv cov qauv raum tsis ua haujlwm.

Daim duab 2Kev hloov hauv kynurenine txoj hauv kev thaum lub raum mob. Nyob rau hauv cov kab mob raum ntev tau pom tias qis dua cov ntshav siab ntawm Trp nyob rau hauv ob qho tib si, tsiaj txhu thiab tib neeg kev tshawb fawb. Hloov pauv, cov ntshav siab dua KYN, KYNA, 3-OHKYN, AA, XA, thiab QA tau tshaj tawm, qhia txog kynurenine txoj hauv kev ua kom muaj kab mob raum ntev. 3-OHKYN 3-hydroxykynurenine, AA anthranilic acid, IDO indoleamine 2, 3-dioxygenase, KAT kynurenine aminotransferase, KYN kynurenine, KYNA kynurenic acid, QA quinolinic acid, TDO tryptophan 2, }}dioxygenase, Trp tryptophan, XA xanthurenic acid. Tsim nrog BioRender.com

Hauv cov neeg mob uas muaj CKD, plasma Trp tau pom tias txo qis los ntawm 40-60 feem pua; KYN thiab 3-OHKYN nce 32–96 feem pua ​​thiab 184–306 feem pua. Cov ntshav plasma 3-OHKYN / KYN piv tau tshaj tawm tias siab dua li ntawm 40–154 feem pua ​​​​hauv cov neeg mob uraemic, qhov sib piv KYN / Trp tau nce 140–240 feem pua, qhia txog kev ua kom IDO. Ntxiv mus, qhov nce siab ntawm Cu / Zn superoxide dismutase kev ua, tag nrho peroxide, thiab siab C-reactive protein ntau tau pom, thiab KYN nrog 3-OHKYN sib raug zoo nrog cov cim oxidative hauv cov neeg mob CKD. Ib yam li ntawd, Schefold et al. qhia txog kev ua IDO ntau dua hauv cov neeg mob CKD hauv kev koom nrog cov kab mob hnyav thiab qib ntawm cov cim inflammatory, xws li C-reactive protein lossis soluble TNF-receptor-1, raws li tau piav qhia hauv daim duab 2. Kev tswj hwm cov tshuaj lipid-txo qis, uas muaj cov tshuaj tiv thaiv kab mob, txo cov ntshav plasma KYN thiab KYN / Trp piv rau cov neeg mob CKD.

Ntxiv rau qhov pom kev cuam tshuam hauv KYN txoj kev ua haujlwm thaum lub sijhawm CKD, qhov sib txuas ntawm CKD cov teeb meem thiab Trp metabolites tau nthuav tawm hauv ntau qhov kev tshawb fawb (Table 1). Qib ntawm KYN metabolites muaj feem xyuam rau cov tsos mob ntawm lub paj hlwb, tsis muaj erythropoiesis thiab erythrocyte qauv, atherosclerosis, thrombosis, hyperfibrinolysis, thiab pob txha puas thaum lub sij hawm CKD.

Lub tswv yim tshiab txuas rau KYN txoj hauv kev thiab cov kab mob ntsig txog CKD kuj tau tham txog. Trp metabolites, tshwj xeeb tshaj yog KYNA, paub tias endogenous AhR ligands. Muab hais tias AhR activation mediates cardiotoxicity thiab vascular puas tsuaj los ntawm procoagulant thiab prooxidant phenotypes, cov teebmeem ntawm KYN metabolite tsub zuj zuj ntawm cov hlab plawv hauv cov neeg mob CKD tuaj yeem piav qhia los ntawm AhR kev ua haujlwm hloov kho. Ib qho kev sib txuas ntawm AhR ua kom thiab pob txha puas tsuaj hauv CKD tau pom hauv tus qauv tsiaj. Interestingly, lub luag hauj lwm ntawm lub plab microbiota hauv Trp degradation, AhR ua kom, thiabraumfibrosis tsis ntev los no tau tham txog. Kev cuam tshuam hauv plab hnyuv kuj tseem tuaj yeem muaj kev cuam tshuam bidirectional rauraummuaj nuj nqiLos ntawm attenuating inflammatory mob ntawm ib sab tes thiab ua rau insulin tsis kam, tiv thaiv kab mob, thiab atherosclerosis ntawm qhov tod tes.

Thaum kawg, lub luag hauj lwm ntawm ib hom tshwj xeeb ntawmraumKev hloov kho hauv kev txo qis KYN qib thiab lawv cov metabolites tau raug tshuaj xyuas. Txawm hais tias ob qho tib si hemodialysis thiab peritoneal dialysis tau pom tias txo qis ntawm Trp metabolites, lawv cov txiaj ntsig zoo li txawv. Qhov no qhia tau hais tias ob hom kev lim ntshav tsis tuaj yeem kho qhov txawv txav ntawm KYN txoj hauv kev hauv CKD cov neeg mob thiab tsis sib npaug tiv thaiv lawv los ntawm qhov ua tau CKD teeb meem. Tseem ceeb, Yilmaz et al. qhia txog IDO kev ua haujlwm siab dua thiab kev ntxhov siab oxidative hauv cov neeg mob uas tau kuaj ntshav peritoneal piv rau hemodialysis, uas yuav muaj kev cuam tshuam tsis zoo rau chav kawm CKD.

Daim duab 3Cov tshuaj cuam tshuam rau txoj hauv kev kynurenine hauv lub raum. Ob tug IDO inhibitors-BMS{0}} thiab 1-methyl-d-Trp, as Well as KAT inhibitors-angiotensin-hloov enzyme inhibitors, angiotensin II type 1 receptor antagonists, diclofenac thiab gemfibrozil, tsis ntev los no tau piav qhia txog modulators ntawm txoj kev kynurenine hauv lub raum. IDO indoleamine 2,3 dioxygenase, KAT kynurenine aminotransferase, KYN kynurenine, KYNA kynurenic acid, Trp tryptophan. Tsim nrog BioRender.com

Mob ntshav qab zib nephropathy

Mob ntshav qab zib mellitus yog qhov tseem ceeb ntawm CKD thoob ntiaj teb. Qhov tseeb, kwv yees li 30-40 feem pua ​​​​ntawm cov neeg mob ntshav qab zib yuav tsim dmob raum iabetic.Albuminuria tseem yog ib qho kev kuaj thawj zaug rau ntshav qab zib nephropathy. Kev tsom xam Proteomic, suav nrog KYN txoj hauv kev metabolites, yog ib qho kev nthuav dav thiab muaj txiaj ntsig zoo rau kev kuaj mob zoo li no.raumkev puas tsuaj. Thawj qhov kev tshawb pom txog qhov txawv txav hauv KYN txoj hauv kev hauv cov kab mob streptozocin-induced ntshav qab zib nas tau tshaj tawm los ntawm Smith thiab Pogson, uas tau soj ntsuam kev ua haujlwm ntawm TDO thiab KZ ntau ntxiv hauv cov kab mob siab ntawm cov tsiaj mob ntshav qab zib hom 2.5- quav thiab 3. {4}} quav, raws li, qhia siab dua degradation ntawm Trp rau KYN metabolites. Lwm txoj kev tshawb fawb tau tshaj tawm tias XA, uas khi rau insulin, thiab QA, uas txo qis proinsulin secretion thiab inhibits insulin tso tawm ua lub luag haujlwm tseem ceeb hauv cov kab mob ntshav qab zib. Interestingly, IDO qhia thiab nws cov enzymatic kev ua ub no tau pom tau upregulated nyob rau hauv tib neeg-tso islets los ntawm IFN-, ua rau kom nce KYN ntau lawm. Cov teebmeem no tau inhibited los ntawm IL-4 thiab 1-alpha-methyl-Trp, IDO inhibitor. Txawm li cas los xij, cov kws sau ntawv tau tsom mus rau lub sijhawm ntawm islet IFN- raug. Lub sij hawm luv luv IFN- cov teebmeem tuaj yeem tiv thaiv kev puas tsuaj cytotoxic, tab sis ntev IFN- raug thiab ntau dhau ntawm Trp metabolites tuaj yeem ua lub luag haujlwm rau kev puas tsuaj ntawm tes. Ib qho kev xav zoo sib xws tau nthuav tawm los ntawm Oxen ntaub pua plag, qhia tias mob o, koom nrog hauv pathogenesis ntawm tag nrho cov khoom ntawm metabolic syndrome, nrog rau cov ntshav qab zib mellitus, ua rau 'superinduction' ntawm IDO, nrog rau TDO, thiab overactivation ntawm KYN txoj kev.

Hauv cov neeg mob ntshav qab zib, qib siab ntawm KYN, 3-OHKYN, thiab xanthurenic acid (XA) tau kuaj pom hauv cov ntshav thiab zis. Txawm li cas los xij, cov txiaj ntsig ntawm kev tshawb fawb txog ntshav qab zib nephropathy txawv vim muaj ntau haiv neeg ntawm cov tshuaj ntsuam xyuas. Ua ntej, cov ntaub ntawv nthuav tawm txawv ntawm cov hom mob ntshav qab zib tau kuaj. Kev tshuaj ntsuam xyuas ntawm cov cim ntshav hauv cov neeg mob uas muaj ntshav qab zib hom 1 thiab hom 2 qhia qhov sib txawv tseem ceeb ntawm cov pab pawg no. Kev nce qib hauv Trp thiab AA qib tseem ceeb tau pom hauv cov neeg mob ntshav qab zib hom 1, txawm hais tias KYN cov ntsiab lus zoo sib xws ntawm pawg kuaj. KYNA qib ntshav siab dua hauv ob pawg neeg mob ntshav qab zib. Cov kws sau ntawv tau hais tias kev txo qis ntawm IDO los ntawm AA tshwm sim hauv ntshav qab zib hom 1, ua rau Trp nce thiab autoimmune txheej txheem dysregulation. Qhov thib ob, cov txiaj ntsig sib txawv tuaj yeem pom hauv cov neeg mob uas muaj ntau theem ntawm albuminuria thiabraummuaj nuj nqipoob. Piv txwv li, hauv kev tshuaj xyuas ntawm 30 cov neeg mob uas muaj normoalbuminuria thiab 55 (33 nrog ib txwm glomerular filtration rate [GFR] thiab 22 nrog txo GFR) nrog cov tshiab-pib microalbuminuria vim mob ntshav qab zib mellitus hom 1, ntshav ntshav N-formyl KYN qib qis dua hauv cov neeg mob microalbuminuria, tab sis tsis muajraummuaj nuj nqidecline. In contrast, Hirayama et al. performed capillary electrophoresis coupled with time-of-flight mass spectrometry to search for serum markers of diabetic nephropathy with a high level of albuminuria (urine albumin-to-creatinine ratio>300 mg/g). Ntawm 289 metabolites txheeb xyuas, lawv tau txheeb xyuas 19 yam khoom, suav nrog creatinine, aspartic acid, -butyrobetaine, citrulline, symmetric dimethylarginine, KYN, azelaic acid, thiab galactaric acid uas tuaj yeem paub qhov txawv ntawm cov neeg mob thiab tsis muaj albuminuria. Qib KYN cov ntshav tau nce siab hauv cov neeg mob ntshav qab zib nephropathy thiab sib raug zoo nrog cov zis albumin-to-creatinine piv thiab tsis zoo nrog GFR. Nws yuav tsum raug sau tseg tias cov pab pawg neeg mob siab albuminuria kuj muaj ntau duaraummuaj nuj nqidecline, significantly affecting the results presented. Additionally, serum IDO activity was significantly higher in diabetes type 2 patients and closely related to GFR (especially when GFR>60 ml / min / 1.73 m2), tab sis tsis muaj kev cuam tshuam nrog cov neeg mob hnub nyoog. Ntxiv mus, IDO kev ua haujlwm zoo li ua rau muaj ntshav qab zib ntau dua li cov neeg mob glomerulonephritis; Txawm li cas los xij, nws tau qis dua li cov neeg mob uas tau txais hemodialysis, taw qhia txog kev txhaj tshuaj tiv thaiv kab mob siab heev ntawm pab pawg neeg mob no. Tsis tas li ntawd, Oxenkrug tau pom cov qib ntshav siab ntawm KYN, KYNA, thiab XA hauv cov neeg mob ntshav qab zib, qhia tias lawv tuaj yeem siv los ua cov kab mob ntshav qab zib. Hauv cov neeg mob uas muaj CKD tshwm sim los ntawm ntshav qab zib mellitus, plasma Trp theem yog inversely cuam tshuam nrog CKD theem, whereas KYN, KYNA, thiab QA sib cuam tshuam zoo nrog cov kab mob hnyav thiab qis dua.raumlim. Tsis yog TNF- lossis IL-6 tsis cuam tshuam nrog KYN / Trp piv, tab sis TNF- cuam tshuam nrog qib KYN, qhia txog kev ua kom lub cev ua rau mob ntshav qab zib nephropathy. Txawm hais tias Trp thiab KYN / Trp piv tau pom tias muaj feem cuam tshuam nrog albuminuria, tsuas yog KYN / Trp piv tau raug pov thawj los kwv yees cov lus teb rau cov tshuaj txo qis albuminuria nyob rau hauvmob ntshav qab zibraumkab mob.

Ntxiv nrog rau kev kuaj ntshav, cov txiaj ntsig tau nthuav dav tau tshaj tawm hauv kev tshuaj xyuas cov zis hauv cov neeg mob ntshav qab zib hom 2. Cov protein profile ntawm cov zis thaum sawv ntxov kuaj los ntawm cov kua chromatography-mass spectrometry qhia qhov txo qis hauv cov zis Trp thiab KYNA concentrations thiab siab dua KYN qib hauv cov neeg mob ntshav qab zib, tej zaum yog ib feem vim qhov sib txawv ntawm GFRs thiab qis pom ntawm cov metabolites. Tsis tas li ntawd, kev tso zis siab XA tau pom nyob rau hauv cov neeg mob uas muaj ntshav qab zib hom 2 thiab ntshav qab zib hom 2. Cov zis siab KYN, KYNA, XA, thiab QA concentrations thiab siab KYN / Trp piv kuj tseem muaj nyob rau hauv cov neeg mob uas muaj cov kab mob metabolic, tshwj xeeb tshaj yog cov hnub nyoog qis dua 60 xyoo. ntawm hnub nyoog.

Mob raum mob (AKI)

AKI yog ib qho teeb meem tshwm sim heev, tshwj xeeb tshaj yog nyob rau hauv cov neeg mob hauv tsev kho mob, cuam tshuam 57.3 feem pua ​​​​ntawm cov neeg mob hauv cov tsev kho mob hnyav. Kev tuag ntawm AKI yog kwv yees li 26.9 feem pua ​​thiab nce mus txog 55.3 feem pua ​​ntawm cov neeg mob uas xav tau.raumhloov kho. Feem ntau, kev tiv thaiv thiab kev kho mob ntawm AKI yog nyob ntawm seb cov yam ntxwv ntawm lub luag haujlwmraumkev puas tsuaj. Vim muaj cov tsos mob tsis tshwj xeeb thiab ntau qhov chaw kho mob uas txhais tau tias AKI, qhov kev kuaj mob tsim nyog tuaj yeem ncua sij hawm, uas tuaj yeem ua rau rov qab tsis tau.raumkev puas tsuajthiabCKD.Tus qauv ntsuas ntsuas siv los saib xyuas lub raum ua haujlwm, piv txwv li creatinine, tsis muaj txiaj ntsig rau cov neeg laus lossis cov neeg mob tsis noj zaub mov zoo thiab poob sai sailub raum ua haujlwm. Vim tsis pom qhov tshwm sim ntawm kev tshawb fawb hauvAKItsiaj cov qauv thiab tsis muaj peev xwm ntawm AKI biomarkers feem ntau hauv kev kho mob, kev tshawb nrhiav lwm yam AKI ntsuas yog qhov tseem ceeb. Txawm hais tias kev koom tes ntawm KYN txoj hauv kev hauv AKI tau txheeb xyuas, feem ntau cov ntaub ntawv yog los ntawm kev tshawb fawb tsiaj, thiab cov qauv tsiaj sib txawv ntawmAKItuaj yeem ua rau ntau qhov kev txiav txim siab.

Immune-mediated and toxic AKI tseem yog cov qauv AKI tshaj plaws. Saito et al. qhia tau hais tias gerbils raug pokeweed mitogen-induced multiorgan kev puas tsuaj tshwm sim ua rau muaj kev nce hauv lub raum IDO kev ua, ntshav KYN concentration, thiab siab dua cov ntshav qab zib thiab QA qib, qhov kev ua ntawm lwm cov enzymes hauv lub cev.raum, xws li KMO, KZ, KAT, thiab HAAO, tsis tau hloov pauv. Ntawm qhov tod tes, Zheng et al. pom zooraummuaj nuj nqithiab txo cov tubular puas thiab macrophage infiltration hauv KMOnull nas tom qab lub raum ischemia-reperfusion raug mob. Hauv cisplatin-induced AKI hauv C57BL/6 nas, galectin 3 qhia ntawm lub raum dendritic hlwb tau pom los tiv thaiv.raumkev puas tsuajlos ntawm kev txhawb nqa tus neeg hu xov tooj zoo li -2-de pendent activation ntawm IDO thiab KYN txoj hauv kev hauv lub raum dendritic hlwb. Ntxiv mus, ntau dua expansion ntawm Tregs nyob rau hauv raug moblub raumtau pom, taw qhia rau ib qho kev nthuav dav ntawm cisplatin-induced AKI nrog rau lwm yam kev muaj peev xwm ntawm kev tiv thaiv kab mob.raumraug mobtiv thaiv.

Zgoda-Pols et al. qhia tau tias KYN thiab KYNA cov ntshav cov ntshav tau nce siab hauv cov qauv tshuaj lom AKI ntawm cov nas nrograumkev puas tsuajtshwm sim los ntawm cov nicotinic agonist SCH 900424. Ib yam li ntawd, cov ntshav nce siab KYN qib tau tshaj tawm hauv glycerol-induced AKI hauv cov nas, uas tej zaum yuav ua rau KYNA nce, raws li kev ua haujlwm ntawm ntau cov tshuaj tiv thaiv cov proteins, paub tias raug thaiv los ntawm KYNA, raug inhibited. . Hauv gentamicin-induced AKI hauv cov nas, pom muaj qib Trp siab dua, thaum KYNA concentration hauv cov zis txo qis, uas tej zaum yuav yog ib feem cuam tshuam rau lub raum tsis ua haujlwm thiab qis dua KYNA pom tus nqi. KYNA kuj tau raug txheeb xyuas tias yog biomarker ntawm AKI tshwm sim los ntawm arystocholic acid thiab mercuric chloride. Txawm hais tias muaj cov ntaub ntawv tsawg, KYNA tuaj yeem suav tias yog tus neeg saib xyuas nephroprotective. Hauv ischemia-reperfusion AKI hauv nas, KYNA, ua ke nrog ketamine thiab magnesium sulfate, tau pom tias ua rau lub raum tsis zoo thiab oxidative kev nyuaj siab. KYNA kuj tau pom tias tiv thaiv AKI hauv cov nas uas raug cua sov.

Raws li kev tshawb fawb tsiaj, cov ntaub ntawv hais txog qhov tseem ceeb ntawm KYN txoj hauv kev hauv AKI hauv tib neeg raug txwv vim kev xav txog kev coj ncaj ncees. Cov txiaj ntsig zoo siab hais txog KYN txoj hauv kev sib piv rau nephropathy tau luam tawm los ntawm Reichetzeder li al.. Hauv kev tshawb fawb yav tom ntej, 245 tus neeg mob tau ua raws li 120 hnub tom qab kev sib piv cov xov xwm thaum lub sij hawm coronary angiography. Txawm hais tias ua ntej kev cuam tshuam cov ntshav hauv KYN qib tsis cuam tshuam nrog kev pheej hmoo siab ntawm AKI, KYN concentration tau cuam tshuam nroglub raum ua haujlwmkev puas tsuaj nyob rau hauv kev soj ntsuam mus sij hawm ntev. Ntawm qhov tod tes, ntawm cov neeg mob hnyav nrog AKI, urinary Trp, KYN, AA, serotonin concentration, thiab KYN / Trp piv tau qis dua hauv ib pab pawg nrog lig-/ tsis zoo.lub raum ua haujlwm, txawm tias KYNA qib zis tau pom. Ntxiv mus, KYNA tau txuam nrog AKI theem siab dua, ntev AKI ntev, qhov xav tau rau kev kho mob raum, thiab 30- hnub tuag. Ib yam li ntawd, Dąbrowski et al. pom cov ntshav siab KYNA qib hauv cov neeg mob septic shock nrog AKI kom nruj nrog cov txiaj ntsig thiab kwv yees tias kev tuag ntau dua.

Glomerulonephritis - mob

Glomerulonephritis yog ib qho ntawm feem ntau ua rau CKD. Ua kom muaj zog ntxiv thiab mob ntev ua rau cov ntaub so ntswg fibrosis yog cov txheej txheem tseem ceeb ntawm kev raug mob glomerular. Hauv ntau qhov xwm txheej, qhov ua rau glomerular puas tuaj yeem tsim tsis tau, thiab cov txheej txheem pathogenic tsis tuaj yeem rov qab los, txawm tias siv cov tshuaj tiv thaiv kab mob dav dav. Cov hom phiaj glomerular tshiab tuaj yeem pab txhim kho kev kuaj mob thiab kev kho mob, nrog rauraumbiopsy thiab muaj cov cim serological, xws li phospholipase A2 receptor antibodies hauv membranous nephropathy. Kev nce qib ntawm cov ntshav KYN hauv cov neeg mob glomerulonephritis thiab ib txwm muajraum muaj nuj nqitau tshaj tawm; Qhov siab neopterin concentration tau pom ib txhij, qhia txog kev koom tes hauv kev tiv thaiv kab mob hauv KYN txoj kev ua kom. Hauv kab lis kev cai mesangial hlwb, Yoshimura li al. qhia tau tias AA thiab 3-OHKYN txwv tsis pub muaj kev loj hlob tab sis QA thiab KYN txhawb kev loj hlob, txawm tias tsis muaj ntau dua. Hauv tus qauv tsiaj ntawm immunoglobulin A (IgA) nephropathy, Yang li al. pom tias intraperitoneally tswj IDO inhibitor 1-methyl-Trp nce raum puas thiab IgA txuam nrog hauv glomeruli thiab upregulated Th/Treg qhia thiab cytokine tso. Hauv qhov sib piv, IDO agonist ISS-ODN txo qis rau cov ntaub so ntswg puas thiab IgA tsub zuj zuj, nrog rau Th17-kho cytokine, hloov pauv hauv IgA nephropathy qauv. Nyob rau hauv tib neeg nrog biopsy-proven IgA nephropathy, urinary AA cuam tshuam nrog proteinuria, ua rau nws muaj peev xwm tsis muaj peev xwm biomarker ntawm proteinuria hnyav.

Kev koom tes ntawm KYN hauv mesangioproliferative glomerulonephritis kuj tau tham txog. Hauv cov qauv tsiaj ntawm crescentic glomerulonephritis thiab nephrotoxic serum nephritis, Hou et al. tau soj ntsuam kev ua haujlwm ntawm IDO ntau ntxiv (los ntawm KYN / Trp piv) hauv cov ntshav thiab lub raum cov ntaub so ntswg thiab txhawb nqa IDO cov noob qhia hauv glomeruli thiab tubular epithelial hlwb. Ntxiv mus, 1-methyl-Trp nce glomerular crescent tsim, macrophage infiltration, thiab intrarenal cell proliferation, ho stimulating.

nephritis kev loj hlob. Ib yam li ntawd, cov ntshav siab KYN qib nrog txo qis Trp concentrations tau pom nyob rau hauv cov neeg mob uas muaj antineutrophil cytoplasmic antibody-associated vasculitis, ib qho ntawm cov ua rau glomerulonephritis sai sai nrog crescent tsim. Hauv cov qauv autoimmune glomerulonephritis hauv Wistar-Kyoto nas, ib qho qauv ntawm anti-glomerular hauv qab daus membrane glomerulonephritis, 3-OHAA thiab 3-OH KYNA tau pom tias yuav txo qis glomerular puas thiab inflammatory cell infiltration, txo proteinuria thiabtxhim khoraummuaj nuj nqi. Cov kev tshawb fawb no muab pov thawj tseem ceeb ntawm KYN txoj kev koom tes hauv glomerulonephritis pathogenesis; Txawm li cas los xij, ntau cov ntaub ntawv tsis muaj, tshwj xeeb tshaj yog hais txog kev tiv thaiv kab mob membranous nephropathy los yog focal segmental glomerulosclerosis, uas yog cov teeb meem nrog kev kho mob hnyav, kev hloov pauv hloov mus rau kev tiv thaiv kab mob thiab tsis paub tseeb.

Hloov pauv raum

Kev hloov pauv raum tseem yog hom kev kho raum hloov kho rau CKD. Ib qho kev nce ntxiv hauv kev ua neej zoo thiab muaj sia nyob tom qabraumhloov pauvHauv kev sib piv nrog cov neeg mob hemodialysis tau rov ua pov thawj. Txawm li cas los xij, nws yuav tsum raug sau tseg tias qhov kev pheej hmoo ntawm kev kis tus kab mob kis tau zoo thiab mob qog noj ntshav vim yog kev siv tshuaj tiv thaiv kab mob tuaj yeem txwv cov txiaj ntsig hauv qee cov neeg mob. Lwm qhov teeb meem tseem ceeb yograumhloov pauvKev tsis lees paub vim tias kev tiv thaiv kab mob tsis txaus, kev kis tus kab mob kis tau zoo dua, thiab rov tshwm sim thawj zaugraumkab mob. Qhov no qhia txog qhov yuav tsum tau tshawb nrhiav tshiab serological, tso zis, thiab cov cim histological los kwv yees cov txiaj ntsig tom qab hloov lub raum. Vim tias KYN txoj hauv kev ua haujlwm tau tswj hwm los ntawm kev tiv thaiv kab mob, nws yog lub hom phiaj nthuav dav los saib xyuas lub raum kev ua haujlwm. Piv txwv li, Myśliwiec et al. tau pom ntau dua ntawm cov ntshav plasma KYN metabolite qib hauv cov neeg tau txais kev hloov hauv lub raum, txawm tias qis dua hauv cov neeg mob ntawm hemodialysis. Txawm hais tias muaj kev cuam tshuam tsis zoo ntawm Trp thiab creatinine concentration, qhov kev sib raug zoo tau pom ntawm Trp thiab GFR hauv cov neeg mob no, qhia tias Trp degradation ntau dua thaumraummuaj nuj nqideteriorates. Tsis tas li ntawd, txoj kev tshawb no tau pom tias kev hloov lub raum tau txo qis KYN qib piv nrog cov neeg mob CKD. Cov kev tshawb pom zoo sib xws tau tshaj tawm los ntawm Lahdou et al., uas tau soj ntsuam cov ntshav plasma KYN qis dua hauv cov neeg mob tom qab.raumhloov pauv. Ntxiv mus, nws tau pom tias qhov nce hauv KYN qib tom qab hloov pauv tau kwv yees qhov mob raum tsis zoo tab sis qhov nce ua ntej.raumimplantation tsis muaj lub luag haujlwm hauvraum muaj nuj nqikwv yees. Ib yam li ntawd, Holmes et al. tau tshaj tawm cov qib siab ntawm cov ntshav KYN hauv cov neeg mob uas muaj kev tsis haum tshuaj loj lossis thaum kis kab mob los yog kab mob. Txawm hais tias KYN concentration zoo li tsis muaj feem cuam tshuam nrog creatinine concentration thiab tsis cuam tshuam los ntawm kev kho corticosteroid, hauv kev tshuaj xyuas rov qab, KYN tau ua pov thawj tias yog ib qho txiaj ntsig zoo ntawm lub raum tsis lees paub nrog rau cov ntshav creatinine qib. Vim tias IDO ua kom los ntawm IFN- depletes Trp thiab suppresses T-cell mediated kev tiv thaiv, lub luag haujlwm ntawm IDO hauv lub raum graft tswj tau txheeb xyuas los ntawm Brandacher li al.raum hloov pauvCov neeg mob, txawm hais tias cov ntshav thiab zis KYN / Trp piv tau zoo heev hauv kev tsis lees txais cov khoom noj. Qhov tseem ceeb, IDO immunostaining siab dua tau kuaj pom hauv kev tsis lees paubraumbiopsies, tshwj xeeb tshaj yog nyob rau hauv tubular epithelial hlwb. Raws li 2- xyoo rov qab, VavrincovaYaghi et al. pom tias ob qho tib si hauv cov ntshav thiab cov zis KYN / Trp piv tuaj yeem pab tau rau kev saib xyuas kev ua haujlwm ntev ntev. Hauvraumbiopsies tau ua tom qab 2 xyoos nyob rau hauv cov neeg mob uas muaj yav dhau los mob, ciam teb, los yog ntev allograft rejection, IDO tau mas pom nyob rau hauv inflammatory cells thiab glomeruli, correlating nrog rau cov ntshav thiab zis. Hauv lwm txoj kev tshawb fawb ua los ntawm de Vries li al., ntshav qab zib 3-OHKYN yog qhov muaj zog tshaj plaws ntawm kev ua tsis tiav thiab kev tuag ntawm tus neeg mob, thiab Minović li al. tau tshaj tawm tias muaj kev pheej hmoo ntawm kev tuag ntau ntxiv vim mob qog noj ntshav lossis kis kab mob ntxiv rau kev sib raug zoo ntawm 3-OHKYN thiab raum graft tau txais kev tuag tag nrho.

Kev sib raug zoo ntawm cov kab mob kis tom qabraumKev hloov pauv thiab txoj hauv kev KYN tau txheeb xyuas hauv kev tshawb fawb los ntawm Sadeghi li al.. Contrary to polyomavirus BK, cytomegalovirus kab mob tau cuam tshuam nrog ntau dua plasma KYN thiab QA ntau ntxiv nrog rau kev mob hnyav. Txhawm rau pab kom sib txawv ntawm kev tsis lees txais kev ua txhaum loj thiab kev kis mob hnyav, Dharnidharka li al. tau kawm txog 29 tus menyuam uas tau txais araumhloov pauv hauv 1 xyoos ntawm kev soj ntsuam; Txawm hais tias cov ntshav qab zib KYN / Trp piv tau ntau dua rau cov neeg uas tau ntsib kev tsis txaus siab ntawm kev ua txhaum cai, cov ntshav CD4- qib ATP tau txais txiaj ntsig zoo hauv kev kuaj mob sib txawv, vim tias lawv qis dua hauv pab pawg uas muaj kab mob. Tsis tas li ntawd, Kaden et al. pom cov ntshav plasma ntau dua KYN hauvraumgraft tau txais nrog cytomegalovirus kab mob thiab nws txoj kev sib raug zoo nrog tus kab mob hnyav.

Tsis zoo li qhov kev tshawb pom yav dhau los, muaj qee cov ntaub ntawv sib cav txog kev sib txuas ntawm KYN txoj hauv kev thiab kev tsis lees txais nyiaj txiag. Nyob rau hauv ib qho kev tshawb nrhiav rov qab uas muaj 307raumCov neeg tau txais txiaj ntsig, tsis muaj kev sib koom ua ke ntawm KYN concentration thiab cov kab mob hauv lub raum thawj, kev tsis lees txais cov khoom plig, lossis kev ciaj sia. Txawm li cas los xij, pretransplant KYN qib tau siab dua hauv cov neeg mob uas muaj kab mob-reactive antibody-zoo thiab cov neeg tos ntev dua ntawm daim ntawv hloov pauv. Ntawm qhov tod tes, qhov qis dua pretransplant KYN concentration yog cuam tshuam rau kev ua haujlwm ntawm kev ua haujlwm sai dua. Txawm hais tias cov txiaj ntsig ntawm txoj kev tshawb no taw qhia txog kev sib txuas ntawm KYN txoj hauv kev thiab kev txhaj tshuaj tiv thaiv ntawm cov neeg mob ua ntejraumhloov pauv, txoj kev tshawb no tau ua nrog kev siv cov txheej txheem photometric los ntsuas cov qib KYN thiab tsis yog qhov siab-rhiab heev ua kua chromatography lossis kua chromatography-mass spectrometry, raws li nyob rau hauv feem ntau cov kev tshawb fawb, uas tej zaum yuav yog ib qho tseem ceeb txwv ntawm daim ntawv qhia no.

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