Kev cai ntawm Pericyte Metabolic Reprogramming Inhibits Kev Txhim Kho Ntawm AKI rau CKD

Mob raum raug mob (Acute Kidney Injury, AKI) feem ntau nrog rau kev mob siab thiab kev tuag thiab yog ib qho kev pheej hmoo mus sij hawm ntev rau kev loj hlob ntawm Chronic Kidney Disease (CKD). Interstitial fibrosis thiab proliferation ntawm myofibroblasts yog cov yam ntxwv pathological ntawm AKI nce mus rau CKD. Pericytes yog qhov loj ntawm myofibroblasts hauv lub raum fibrosis. Txawm li cas los xij, cov txheej txheem hauv qab ntawm pericyte-to-myofibroblast kev hloov pauv (PMT) tseem tsis meej. Cov kws tshaj lij Chen Xiangmei pab pawg los ntawm PLA General Tsev Kho Mob tau pom tias fatty acid oxidation tau txo qis thiab glycolysis tau nce- tswj thaum PMT.

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Nyem rau cistanche herba rau mob raum

Tsis tas li ntawd, PGCl activator ZLN-005 tuaj yeem qhib FAO lossis hexokinase 2 (hexokinase 2, HK2) inhibitor 2-DG los inhibit glycolysis, ob qho tib si tuaj yeem inhibit PMT thiab ncua kev nce qib ntawm AKI rau CKD. Mechanistically, AMPK yog cov khoom siv hluav taws xob uas tswj kev hloov pauv ntawm glycolysis rau FAO metabolism; tshwj xeeb, nws txhawb FAO los ntawm kev ua kom cov lus qhia ntawm PGCl -CPT1A thiab inhibits glycolysis los ntawm inhibiting qhov qhia ntawm HIF1 -HK2, yog li inhibiting PMT.

1. Hauv AKI-CKD, pericytes transdifferentiate rau hauv myofibroblast pericytes, uas yog mesenchymal-derived hlwb uas feem ntau qhia platelet-derived growth factor (PDGFR-), chondroitin sulfate proteoglycan (NG2) thiab Cell nto glycoprotein (CD146). Cov txiaj ntsig ntawm immunofluorescence colocalization tau pom tias hauv AKI-CKD, PDGFR- ntxiv -SMA ntxiv, CD146 ntxiv -SMA ntxiv, thiab NG2 ntxiv -SMA ntxiv cov hlwb tau nce zuj zus, thiab pericytes tau hloov pauv mus rau hauv myofibroblasts.

cistanche herba

2. Hauv AKI-CKD, FAO ntawm pericytes yog qhov tsis zoo thiab qib ntawm glycolysis yog nce. Tom ntej no, kom paub meej txog cov txheej txheem ntawm pericyte transdifferentiation hauv AKI-CKD, tus sau tau txheeb Sham, uIRI-2d, uIRI-7d, thiab uIRI-14d PDGFR- ntxiv rau pericytes thiab raug rau transcriptome sequencing. Cov txiaj ntsig ntawm GSEA tsom xam pom tias nyob rau hauv AKI-CKD, cov kev taw qhia txog kev muaj feem xyuam rau fatty acid oxidation ntawm PDGFR-ntxiv pericytes, Mitochondrial fatty acid beta-oxidation, thiab fatty acid metabolism, tau txo qis-tswj. Glycolysis-hais txog cov noob caj noob ces tau tswj hwm tau zoo.

Tsis tas li ntawd, cov kws sau ntawv tau lees paub ntxiv cov txiaj ntsig ntawm kev sau cov ntaub ntawv los ntawm qPCR thiab immunofluorescence co-staining. Cov kws sau ntawv pom tias hauv AKI-CKD, kev qhia ntawm fatty acid oxidation transcription factor PGC1 hauv NG2 ntxiv rau pericytes tau txo qis thiab kev qhia ntawm glycolytic tseem ceeb enzyme HK2 tau nce ntau.

3. PGC1 activator ZLN-00 tsub kom FAO thiab inhibits pericyte transdifferentiation Txhawm rau ntxiv kom meej lub luag haujlwm ntawm fatty acid oxidation hauv pericyte transdifferentiation, tus sau tau muab PGC1 activator ZLN-005 thiab tom qab ntawd txheeb tawm ZLN-005 Kev kho mob Tom qab 7 hnub thiab 14 hnub, PDGFR-ntxiv rau pericytes tau txheeb xyuas los ntawm kev sib sau ua ke. Tus sau tau pom tias tom qab 7 hnub thiab 14 hnub ntawm PGC1 activator ZLN-005, cov kev taw qhia txog kev muaj feem xyuam rau cov roj acid oxidation hauv PDGFR-ntxiv rau pericytes, Mitochondrial fatty acid beta-oxidation, thiab fatty acid metabolism, tau nce siab- kev tswj hwm, thiab txoj hauv kev cuam tshuam txog fibrosis tau ua tau zoo heev. nqes.

cistanche dose

Tsis tas li ntawd, cov kws sau ntawv tau lees paub ntxiv cov txiaj ntsig ntawm kev sib sau ua ke nrog qPCR thiab immunofluorescence co-staining. Cov kws sau ntawv pom tias ZLN-005 tuaj yeem ua rau muaj kev nthuav qhia ntawm PGC1 hauv NG2 ntxiv rau pericytes, nce qib ntawm FAO hauv pericytes, thiab txo qis raum lipid deposition.

4. HK2 inhibitor 2-DG inhibits glycolysis thiab pericyte transdifferentiation Txhawm rau nthuav dav ntxiv lub luag haujlwm ntawm glycolysis hauv pericyte transdifferentiation, tus sau tau muab glycolysis tseem ceeb enzyme HK2 inhibitor 2-DG thiab txheeb xyuas Transcriptome sequencing tau ua ntxiv rau ntawm PDGFR- pericytes muab tshuaj rau 7 thiab 14 hnub.

Cov kws sau ntawv pom tias glycolysis-hais txog cov noob thiab cov noob muaj feem cuam tshuam nrog fibrosis tau txo qis tom qab 7 thiab 14 hnub ntawm 2-DG kho. Tsis tas li ntawd, cov kws sau ntawv tau ua pov thawj ntxiv cov txiaj ntsig ntawm transcriptome sequencing. Cov kws sau ntawv pom tias 2-DG tuaj yeem cuam tshuam qhov kev qhia ntawm HK2 hauv NG2 ntxiv rau pericytes thiab inhibit qhov nce ntawm uIRI-induced hauv pericyte glycolysis.

cistanche tubulosa side effects

5. AMPK yog ib qho tseem ceeb ntawm cov molecule uas tswj kev hloov pauv ntawm pericyte glycolysis rau FAO. AMPK ua lub luag haujlwm tseem ceeb hauv kev tswj hwm ntawm cellular zog homeostasis. Cov kev tshawb fawb tau pom tias hauv AKI-CKD, AMPK tswj qhov tshwm sim ntawm lub raum fibrosis. Cov kws sau ntawv tau tshawb nrhiav ntxiv seb AMPK puas koom nrog hauv cov metabolic reprogramming ntawm pericytes. Nws tau pom tias AMPK tswj cov kev qhia ntawm PGC1 / CPT1A hauv pericytes, nce FAO, thiab tib lub sijhawm inhibits kev qhia ntawm HIF1 / HK2 hauv pericytes thiab inhibits glycolysis.

Lub Mechanism ntawm Cistanche Kho raum kab mob

Cistanche yog cov tshuaj ntsuab ib txwm siv hauv Suav teb rau kev kho mob raum, tshwj xeeb tshaj yog mob raum tsis txaus. Cistanche muaj ntau yam bioactive tebchaw, suav nrog phenylethanoid glycosides, iridoids, lignans, thiab polysaccharides, uas ua haujlwm ntau yam tshuaj, xws li tshuaj tiv thaiv, tiv thaiv oxidative, thiab immunomodulatory teebmeem.

Lub tshuab ntawm Cistanche hauv kev kho mob raum muaj ntau yam:

Txhim kho lub raum hemodynamics: Cistanche tuaj yeem ua rau kom cov ntshav khiav thiab txhim kho glomerular filtration rate (GFR), yog li txhim kho lub raum ua haujlwm.

Txo oxidative kev nyuaj siab: Cistanche muaj cov tshuaj tiv thaiv kab mob antioxidant uas tuaj yeem tshem tawm cov dawb radicals thiab txo oxidative kev nyuaj siab, uas yog ib qho tseem ceeb ntawm qhov pib thiab kev loj hlob ntawm cov kab mob raum.

Inhibiting o: Cistanche tuaj yeem cuam tshuam qhov tso tawm ntawm cov kab mob cytokines thiab chemokines, uas tuaj yeem txo qhov mob hauv lub raum thiab tiv thaiv kev puas tsuaj ntxiv.

Tiv thaiv lub raum hlwb: Cistanche tuaj yeem tiv thaiv lub raum hlwb los ntawm kev puas tsuaj los ntawm ntau yam xws li co toxins, ischemia / reperfusion raug mob, thiab kev laus.

Modulating lub cev tiv thaiv kab mob: Cistanche tuaj yeem tswj lub cev tiv thaiv kab mob thiab txhim kho lub cev tiv thaiv kab mob thiab mob.

Zuag qhia tag nrho, Cistanche tuaj yeem txhim kho lub raum ua haujlwm thiab txo qis kev mob raum vim nws cov txiaj ntsig zoo ntawm lub raum hemodynamics, oxidative stress, o, raum cell tiv thaiv, thiab kev tiv thaiv kab mob.