Mitochondrial Membrane Stabilization Los ntawm Angelica Sinensis Polysaccharide hauv Murine Aplastic Anemia
Mar 16, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
Abstract
Txhawm rau tshawb xyuas cov txheej txheem ntawm mitochondrial membrane stabilization los ntawm Angelica Sinensis polysaccharide (ASP) hauv murine aplastic anemia (AA) ICR nas tau muab faib rau hauv kev tswj hwm. AA thiab ASP-kho pab pawg AA pawg nas tau kho nrog 60Co Y thiab intraperitoneal txhaj ntawm cyclophosphamide thiab chloramphenicol. Cov tsiaj tswj tau raug kho nrog cov hlau lead shielding irradiation thiab saline txhaj tshuaj. Cov nas AA kho tau noj nrog ASP rau 2 wk. Mitochondrial ultrastructure ntawm cov pob txha pob txha tau pom los ntawm kev sib kis ntawm electron microscopy, thiab transmembrane muaj peev xwm ntawm cov pob txha pob txha-nucleated hlwb (BMNC) tau tshuaj xyuas los ntawm fluorescence spectrophotometric. Cox thiab MDH cov ntsiab lus ntawm qhov nruab nrab kuj tau kawm nyob rau hauv peb pawg, Tus lej mitochondrial thiab transmembrane peev xwm ntawm BMNC hauv cov pob txha pob txha poob qis hauv pawg AA piv rau pawg tswj tab sis txhim kho hauv pawg ASP-kho zoo li piv rau pawg AA. Ua tiav mitochondrial cleavage nyob rau hauv pab pawg neeg kho ASP tau qeeb qeeb (P< 0.05)="" as="" compared="" to="" the="" aa="" group.="" we="" conclude="" that="" asp="" might="" improve="" mitochondrial="" membrane="" stabilization,="" and="" suppress="" the="" downregulation="" of="" transmembrane="" potential="" and="" apoptosis="" of="" bmnc="" in="">
Hot Tags: aplastic anemia, Angelica Sinensis polysaccharide, mitochondria, daim nyias nyias, ICR nas
cistanche extract: boosts pob txha tsim thiab nce pob txha ceev
Keeb kwm
Aplastic anemia (AA) yog ib yam kab mob ntshav uas cov pob txha pob txha thiab cov qe ntshav txuam raug puas tsuaj ua rau cov qe ntshav liab tsis txaus, cov qe ntshav dawb, thiab cov platelets. Cov kev tsis zoo no yog tus kheej lub npe hu ua anemia, leukopenia, thiab thrombocytopenia, feem, thiab suav ua ke hu ua pancytopenia. Raug tshuaj, tshuaj, hluav taws xob, cov khoom siv hluav taws xob, cov khoom siv hluav taws xob tsim hluav taws xob, kev kis kab mob. kab mob tiv thaiv kab mob, heredity (hauv 50 feem pua ntawm cov neeg mob) thiab tsis paub txog etiology kuj tuaj yeem ua rau kev loj hlob ntawm AA.
Mitochondria raug suav hais tias yog "lub zog ntawm tes" vim tias lawv tsim adenosine triphosphate (ATP) los ntawm kev rho tawm lub zog los ntawm cov khoom noj khoom haus molecules (substrates) [1]. Ntxiv mus, mtDNA yog replicated nrog ib tug siab hloov pauv vim nws tsis muaj kev tiv thaiv histones thiab ib tug zoo DNA kho system. Kev hloov pauv hauv mtDNA cuam tshuam nrog cov kab mob hematological xws li kis tau tus mob sideroblastic anemia, myelodysplastic syndromes, thiab tau txais AA [2-4]. Peb txoj kev tshawb fawb yav dhau los 5] tau pom tias kev ua haujlwm tsis zoo ntawm mitochondrial respiratory chain induced los ntawm kev hloov pauv tuaj yeem koom nrog hauv hematopoietic tsis ua haujlwm hauv AA cov neeg mob. Tsis hais txog cov yam ntxwv morphological ntawm lub sijhawm kawg ntawm tes tuag (apoptotic, necrotic, autophagic, lossis mitotic), mitochondrial membrane permeabilization (MMP) feem ntau yog qhov kev txiav txim siab ntawm kev ciaj sia thiab kev tuag [6]
Raws li cov tshuaj suav tshuaj, Angelica Sinensis pab ua kom cov ntshav sib koom ua ke thiab txhawb nws txoj kev ncig [7]. Cov kev tshawb fawb tsis ntev los no tau pom tias cov extracts ntawm Angelica Sinensis muaj cov tshuaj tiv thaiv oxidative thiab neuroprotective [8,9]. Txawm li cas los xij, kev ua haujlwm tiv thaiv oxidative ntawm ASP tseem tsis meej. Txoj kev tshawb no tau tshuaj xyuas qhov kev puas tsuaj ntawm tes thaum ntxov siv mitochondrial lysis lub sij hawm nkhaus thiab mitochondrial membrane-stabilizing nyhuv ntawm ASP hauv AA.
cistanche ntxiv ua kom cov pob txha ceev thiab boosts pob txha tsim
Cov ntaub ntawv thiab cov txheej txheem
Pab pawg tsiaj
Noj qab nyob zoo ICR txiv neej nas, hnyav 18-22 g, hnub nyoog 6-8 lub lis piam, tau muab los ntawm Kev Tshawb Fawb Tsiaj Center ntawm Shandong University (Tuam Tshoj). Tsiaj txhu tau nyob rau hauv ib qho chaw sov, nyob ntsiag to nrog kev nkag tau dawb rau zaub mov thiab dej. thiab acclimatized rau ib lub lis piam ua ntej pib qhov kev sim.
Cov nas tau muab faib ua peb pawg: pawg ib txwm, pawg AA, thiab pab pawg kho, raws li. Tus qauv aplastic anemia tau tsim raws li tau piav qhia yav dhau los [10].
Luv luv, cov nas tau irradiated nrog 2.0Gy 60Coy thiab tom qab ntawd kho nrog kev txhaj tshuaj intraperitoneal txhua hnub ntawm 40 mg / kg / hnub cyclophosphamide thiab 50 mg / kg / hnub chloramphenicol rau peb hnub tom ntej. Cov pab pawg kho mob tau noj intragastrically nrog ASP (200 mg / kg / d, raws li phau ntawv txhais lus Suav Kho Mob). Pawg tswj hwm thiab AA pab pawg nas tau noj intragastrically nrog physiological saline (10 ml / kg / d) noj zaub mov ntxiv. Tsis tas li ntawd, txhua tus nas tau txais kev noj zaub mov zoo thaum kawm. Tom qab kev kho mob nrog ASP los yog physiological saline rau 2 wk, cov nas tau txi los ntawm lub ncauj tsev menyuam dislocation.
Kev kuaj ntshav hematological
Cov ntshav qog ntshav los ntawm peb pawg tau sau rau thawj hnub thiab kaum plaub hnub, raws li. WBC thiab platelets tau suav hauv cov qauv ntshav peripheral, thiab qib Hb tau txiav txim siab. Thaum ua tiav cov kev sim, cov nas tau muab txi thiab femur smears tau npaj rau kev suav qhov sib txawv ntawm cov pob txha pob txha-nucleated hlwb (BMNCs) (Daim duab 1).
Kev xa tawm electron microscopy
Lub femoral marrow tau smeared thiab hlais rau hauv ultrathin seem. Mitochondria ntawm hematopoietic hlwb nyob rau hauv femoral marrow tau soj ntsuam thiab suav los ntawm kev xa hluav taws xob microscopy (JEM-2000EX, Nyiv) hauv qab 50 thaj chaw ntawm kev pom.
Mitochondrial lysis lub sij hawm nkhaus
Mitochondria tau muab rho tawm los ntawm murine BMNCs raws li cov chaw tsim khoom raws tu qauv ntawm mitochondria cais cov khoom siv (Pierce Biotechnology Inc., USA). Cov concentration ntawm monoamine oxidase (MAO) qhia qhov concentration ntawm mitochondria thiab tau txiav txim siab siv 200U / ml mitochondrial ncua kev kawm ntawv los ntawm 20 cov kab lis kev cai, nyob rau hauv 12 teev ntawm lub sij hawm sib txawv (30 min intervals). Cov ntsiab lus ntawm cytochrome oxidase (Cox) thiab malate dehydrogenase (MDH) hauv nruab nrab kuj tau txiav txim siab. Lub sijhawm soj ntsuam lub sijhawm siab tshaj plaws ntawm mitochondrial membrane thiab matrix-specific enzyme concentration-time curves pom qhov ntawm mitochondrial membrane lysis.
Mitochondrial membrane muaj peev xwm
Tom qab ua ntej incubation nrog MAO los yog ASP, cov mitochondria cais tawm los ntawm peb pawg tau resuspended nyob rau hauv 0.5 ml phosphate-buffered saline (Wuhan Boster Biotechnology, Ltd., Tuam Tshoj), thiab 10 ul rhodamine 123 ua hauj lwm tov ( Sigma-Aldrich, TEB CHAWS USA) tau ntxiv thiab incubated ntawm 37 degree C hauv 5 feem pua CO2 rau 15 feeb.
Kev txheeb cais
Kev txheeb cais tau ua tiav siv SPSS 19.0 software. Cov ntaub ntawv yog qhia raws li txhais tau tias thiab tus qauv sib txawv. Cov tub ntxhais kawm qhov t-test tau siv los sib piv cov pab pawg sib txawv. P < 0.05="" raug="" suav="" hais="" tias="" yog="" qhov="" tseem="">
cistanche tshuaj ntsuab: rau cov pob txha zoo
Cov txiaj ntsig
Cov ntshav peripheral thiab BMC suav
Siv lub tshuab ntsuas ntshav tsis siv neeg lub cev tag nrho, tus naj npawb ntawm cov qe ntshav peripheral thiab BMCs hauv AA nas tau pom tias tsis tshua muaj qis (P<0.05), indicating="" that="" the="" aa="" mouse="" model="" was="" successfully="" established="" (table="">
Mitochondrial ultrastructure hauv aplastic anemia nas
Kev xa tawm electron microscopy ntawm cov pob txha pob txha ntawm AA nas tau pom tias mitochondrial ultrastructure tau txhim kho nrog ASP hauv pawg kho mob (Table 2 thiab daim duab 1), qhia tias ASP stabilizes mitochondria hauv AA nas. Qhov loj thiab cov duab ntawm mitochondria ntawm pawg tswj hwm yog qhov qub. Qhov sib txawv. mitochondria ntawm pawg AA tau nthuav dav cov qauv globular, nrog rau kev cuam tshuam lossis ploj ntawm cristae (Daim duab 1A-C).
Mitochondrial membrane muaj peev xwm (MMP) hauv aplastic anemia nas
Raws li kis tau tus mob electron microscopy qhia mitochondrial kev puas tsuaj, peb txiav txim siab qhov cuam tshuam ntawm ASP ntawm MMP hauv AA nas los ntawm kev ntsuas cov txheeb ze sib txawv ntawm cov fluorescence ntawm Rh 123 ntawm peb pawg siv fluorescence spectrophotometer.
Cov txiaj ntsig tau pom tias Rh 123 fluorescence ntawm cov pob txha hlwb hauv pawg AA (19.6 ± 3.03) qis dua li hauv pawg tswj hwm (31.7 ± 2.59, P.<0.0). however,="" the="" rh="" 123="" fluorescence="" of="" the="" asp-treated="" aa="" group="" was="" higher="" than="" that="" in="" the="" aa="" group=""><0.0i)(table 2="" and="" figure="" 2),="" indicating="" that="" asp="" facilitated="" the="" recovery="" of="" the="" mmp="" in="" aa="">
Thaum ntxov cell puas mitochondrial lysis lub sij hawm nkhaus
Hauv pawg tswj hwm, cov ntsiab lus ntawm mitochondrial hauv vitro kab lis kev cai Cox thiab MDH siv sijhawm 3.5 teev kom ncav cuag lub ncov. MAO cov ntsiab lus hauv kab lis kev cai tsis hloov pauv ntau lub sijhawm, tab sis cov ntsiab lus ntawm COX thiab MDH maj mam nce nrog lub sijhawm, ncav cuag lub ncov, thiab tom qab ntawd maj mam poob. Yog li, tag nrho cov ntsiab lus mitochondrial tso tawm los ntawm cov hlwb siv li 3.5 teev kom ncav cuag qhov siab tshaj plaws.
COXand MDH peaks hauv AA pab pawg tau tshwm sim ntawm 1.5 teev, 1.375U /, 36.732U / l, raws li. COX thiab MDH peaks hauv pawg kho mob tshwm sim ntawm 5.5 teev, 6.5 teev, 1.341U / l, 33.994U /, raws li. Ob pawg ntawm cov ntaub ntawv ntawm txhua lub sijhawm taw tes tau siv rau kev txheeb xyuas kev txheeb xyuas. Thaum 1.5 teev, COX thiab MDH qib hauv pawg AA tau nce siab dua hauv pawg kho mob (P < 0.05).="" yog="" li="" ntawd,="" ua="" kom="" tiav="" mitochondrial="" cleavage="" nyob="" rau="" hauv="" cov="" ntshav="" tau="" qeeb="" qeeb="" tom="" qab="" qhov="" sib="" ntxiv="" ntawm="" asp="" (p=""><0.05), nrog="" rau="" lub="" ncov="" me="" ntsis="" (daim="" duab="">
Kev sib tham
Aplastic anemia (AA) yog ib qho mob pob txha tsis ua haujlwm uas tshwm sim los ntawm peripheral pancytopenia thiab pob txha hypoplasia. Kev hloov pauv thiab tsis ruaj khov ntawm mtDNA tau tshwm sim hauv ntau yam kab mob. Mitochondrial dysfunction thiab txo tus naj npawb ntawm mitochondria tuaj yeem ua rau txo qis ntawm mtDNA, Tau txais kev tshem tawm ntawm mtDNA hauv hematopoietic compartment tau pom tshwm sim hauv pancytopenia hnyav thiab reticulocytopenia [11]. Raws li peb cov kev tshawb fawb yav dhau los [5], peb tau tshuaj xyuas seb ASP puas tuaj yeem txhim kho cov mitochondrial membrane ntawm AA nas.
Angelica Sinensis polysaccharide-hlau complex (APIC) tsis yog tsuas yog muaj kev kho mob zoo tshaj plaws ntawm IDA tab sis kuj ntxiv rau cov ntshav thiab txhawb cov ntshav ncig [12]. ASP yuav pab tau rau kev kho mob ntawm cov kab mob tshwm sim los ntawm hepcidin overexpression los ntawm kev tiv thaiv Janus-kinase (JAK), tus tub ntawm leej niam tiv thaiv extracellular decapentaplegic (SMAD) thiab 1signal-regulated kinase (ERK) txoj hauv kev los txo qis hepcidin qhia hauv IDA nas [13 ]. Qin J pom tias ASP tuaj yeem txhim kho proteoglycan (PG) synthesis ntawm chondrocytes hauv nas OA qauv hauv vivo thiab IL-1B-stimulated chondrocytes hauv vitro los ntawm kev txhawb nqa kev qhia ntawm aggrecan thiab GTs koom nrog PG synthesis [14].
Hauv peb txoj kev tshawb fawb, AA tus qauv nas raug ntxias los ntawm kev sib xyaw ntawm acetyl phenylhydrazine, X-rays, thiab cyclophosphamide. Cov nas AA tau pom qhov txo qis hauv cov ntshav peripheral leucocytes, Hb, thiab platelets (Table 1), thiab kev txo qis hauv cov hlwb humeral thiab cov hlwb ua mob rau cov hlwb, uas yog cov yam ntxwv kho mob ntawm AA. Cov nas AA tau kho nrog ASP pom qhov nce ntxiv hauv BM hlwb piv rau AA pawg. Tsis tas li ntawd, tus naj npawb ntawm mitochondria hauv cov hlwb hematopoietic kuj raug cuam tshuam. ASP ua rau muaj tus lej ntawm mitochondria ntau dua hauv pawg kho mob piv rau AA pawg (Daim duab 1). Cov txiaj ntsig no tau pom tias ASP tuaj yeem txhawb cov qog hlwb nucleated proliferation, nce tus naj npawb ntawm mitochondria, thiab stabilize lub mitochondrial membrane hauv AA nas.
Mitochondrial raug mob yog tshwm sim los ntawm mtDNA kev puas tsuaj thiab poob ntawm cov qib ntawm mtRNA transcripts, protein synthesis, thiab mitochondrial muaj nuj nqi, uas yuav ua rau txo qis cellular zog, cuam tshuam ntawm cell signaling, thiab cuam tshuam nrog cellular sib txawv thiab apoptosis. Tsis tas li ntawd, tsis muaj mitochondrial ATP ntau lawm yuav txhawb nqa chromosomal instability [15]. Txij li thaum mtDNA encodes cov khoom ntawm plaub ntawm tsib mitochondrial ua pa complexes, alterations nyob rau hauv mtDNA ua rau cov kab mob mitochondrial [16-18]. Sib nrug los ntawm kab mob mitochondrial, kev hloov pauv hauv mtDNA txuas nrog rau mob qog noj ntshav, ntshav qab zib. kab mob plawv. neurodegenerative ntshawv siab, kab mob hematological xws li leukemia thiab cov txheej txheem ntawm kev laus [19]. Qhov tseem ceeb, mtDNA kev hloov pauv, nrog rau kev txo qis hauv mtDNA tus lej luam, tuaj yeem ua rau kab mob [20, 21]. Nkag siab txog cov txheej txheem ntawm tes rau kev saib xyuas ntawm mtDNA kev ncaj ncees thiab tus lej luam yog qhov tseem ceeb tshaj plaws vim nws tuaj yeem muab lub hom phiaj rau kev kho mob rau kev tiv thaiv thiab kho cov kab mob hematological xws li AA. Cov xwm txheej no kuj tseem yuav ua rau txo qis zog metabolism, uas yuav cuam tshuam rau tus kheej rov ua dua tshiab thiab sib txawv ntawm cov qia hlwb hematopoietic.
Cov kev tshawb pom ntawm txoj kev tshawb fawb tam sim no qhia tau hais tias ASP tuaj yeem txhim kho mitochondrial ultrastructure, thiab txo qis kev tswj hwm ntawm transmembrane muaj peev xwm thiab apoptosis ntawm cov ntsiab lus myeloid los kho cov pob txha tsis ua haujlwm.
Cistanche & cistanche extract: bebefit pob txha
Cov ntaub ntawv
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cistanche extract: boosts pob txha tsim thiab nce pob txha ceev
