Dab tsi ua rau Kev Loj Hlob Ntawm Lub Raum Mob Raum Rau Kab Mob Raum Ntev?
Jun 21, 2023
Mob raum raug mob (AKI) yog ib qho kev kho mob nyuaj uas tshwm sim los ntawm kev poob qis hauv lub raum ua haujlwm los ntawm ntau yam etiologies, feem ntau ua rau muaj xws li lub raum ischemia-reperfusion (IR), nephrotoxin puas, thiab raum thiab ureteral obstruction [1]. Nyob rau hauv xyoo tas los no, nrog rau kev nce ntawm cov kab mob ntev xws li kab mob plawv thiab ntshav qab zib tau coj los ntawm cov neeg laus, thiab kev siv dav dav ntawm kev sib piv cov xov xwm thiab cov tshuaj nephrotoxic, qhov xwm txheej tau nce ntau, cuam tshuam rau 13.3 lab tus neeg mob thoob ntiaj teb txhua xyoo, thiab tuaj yeem ua rau 1.7 lab tus tib neeg tuag Kev tuag yog qhov xwm txheej kub ntxhov thiab mob hnyav hauv kab mob raum [2].
Nyem rau cistanche herba rau mob raum
Yav dhau los, nws tau ntseeg tias qhov kev cia siab ntev ntawm cov neeg mob lub raum rov ua haujlwm tom qab AKI tau zoo, thiab qhov muaj peev xwm ntawm kev tsim kab mob raum ntev (CKD) thiab kab mob raum kawg (ERSD) tsawg heev. Tam sim no, AKI tau raug suav hais tias yog qhov tseem ceeb ntawm kev pheej hmoo rau kev txhim kho CKD. CKD yog ib qho ntawm qhov ua rau tuag sai tshaj plaws thoob ntiaj teb thiab xav tias yuav dhau los ua qhov thib tsib ua rau tuag los ntawm 2040. CKD feem ntau tsis tuaj yeem thim rov qab. Thaum CKD txhim kho mus rau ERSD, cov neeg mob feem ntau yuav tsum tau lim ntshav lossis hloov lub raum los hloov lub raum ua haujlwm [2]. Yog li ntawd, nws yog ib qho tseem ceeb kom tau txais kev nkag siab tob txog cov txheej txheem pathophysiological thiab kev hloov pauv ntawm kev kho mob tsis zoo tom qab AKI los tiv thaiv kev loj hlob ntawm AKI rau CKD thiab txawm tias ERSD.
Ua tsis tiav ntawm lub raum tubular epithelial cell kho
Raws li cov khoom tseem ceeb ntawm lub raum, lub raum tubules thiab tubulointerstitium yog qhov tseem ceeb tshaj plaws tom qab lub raum raug mob. Cov txheej txheem ntawm kev raug mob ntawm tubular yog complex, nrog rau oxidative kev nyuaj siab, cell voj voog ntes, mitochondrial tsis ua hauj lwm, induction ntawm aging-related phenotypes, secretion ntawm inflammatory mediators, epigenetic hloov, thiab lwm yam. (Daim duab 1) [3].
Cov kev tshawb fawb tau pom tias kev rov tsim dua tshiab thiab hloov cov hlwb puas los ntawm kev muaj sia nyob tubular epithelial hlwb (TECs) yog lub ntsiab ntawm kev kho tom qab raug mob. Lub peev xwm loj hlob thiab hloov cov hlwb puas yog qhov qhia txog kev ua tiav ntawm kev kho mob raum. Tsis tas li ntawd, kev puas tsuaj TECs kuj tseem muaj feem cuam tshuam nrog cov lus teb inflammatory, ncaj qha lossis tsis ncaj qha rau qhov tshwm sim thiab kev loj hlob ntawm o thiab fibrosis los ntawm ntau yam txheej txheem. Yog li ntawd, kev tiv thaiv lub raum tubules los ntawm kev raug mob rov qab thiab kho cov tubular kev ua haujlwm zoo yuav yog tus yuam sij rau kev kho cov kab mob raum [4].
Cell voj voog G2/M ntes
Cov kev tshawb fawb yav dhau los tau qhia tias kev cuam tshuam ntawm lub voj voog ntawm tes yuav ua rau muaj kev loj hlob ntawm AKI mus rau CKD, feem ntau yog vim G2 / M raug ntes nyob rau hauv peritubular capillaries (PTC) tom qab AKI ua rau kev kho mob tsis zoo thiab cov fibrosis tom qab. Yang et al. tau pom tias kev rov ua dua tshiab ntawm epithelial txhawb kev txhim kho ntawm kev hloov kho thiab G2 / M-nrhiav TECs tau nce hauv kev raug mob hnyav. Nyob rau tib lub sijhawm, G2 / M-ntaus cov hlwb epithelial ua rau kev ua haujlwm ntawm c-junNH2 davhlau ya nyob twg kinase (JNK), uas ua rau kom cov fibrotic cytokines, thiab kev siv cov JNK inhibitors lossis P53 inhibitors tuaj yeem txo lub raum fibrosis [4. ].
mitochondrial tsis ua haujlwm
Piv nrog rau lwm cov hlwb nyob rau hauv lub raum, proximal tubular hlwb noj ntau zog thiab muaj ib tug loj tus naj npawb ntawm mitochondria, thiab yog cov hlwb feem ntau cuam tshuam los ntawm AKI. Cov kab mob Mitochondrial kuj yog ib qho ntawm AKI thiab CKD. Ntau yam mob hnyav thiab mob ntev tuaj yeem ua rau mitochondrial respiratory chain-derived oxidative stress, ultrastructural abnormalities, nce susceptibility rau apoptosis, instability ntawm mitochondrial DNA, thiab tsub zuj zuj ntawm puas mitochondria. Kev cuam tshuam ntawm mitochondrial homeostasis tuaj yeem ua rau lub raum microvascular raug mob, o, fibrosis, thiab lub raum tsis ua haujlwm.
Nws tau pom tias qhov kev cuam tshuam tsis tu ncua ntawm mitochondrial homeostasis thiab tsis tu ncua tubular puas tom qab AKI impairs lub raum kho thiab ua rau kev loj hlob ntawm CKD. Mitochondrial biogenesis (MB) yog hais txog cov txheej txheem ntawm tsim cov mitochondria tshiab thiab duplicating mtDNA los ntawm kev loj hlob ntawm preexisting organelles, thiab MB kuj tseem ceeb heev rau kev hloov cov mitochondria puas thiab tsis ua haujlwm. Kev ua kom MB yog qhov tsim nyog rau kev nce cov metabolism thiab kev xav tau lub zog thaum lub sijhawm rov qab los ntawm kev raug mob ntawm lub cev. Cov kev tshawb fawb tsis ntev los no tau muab cov pov thawj tseem ceeb uas ua rau MBs puas tuaj yeem ua rau kev kho mob tsis zoo thiab kev mob fibrosis tom qab hauv AKI [2].
kev loj hlob ntawm o
AKI nws tus kheej ua tus kab mob inflammatory uas ua rau mob o thiab lub raum fibrosis. Tseem muaj cov lus teb mob ntev ntev hauv lub raum tom qab AKI, thiab txawm tias lub raum ua haujlwm tau zoo ib nrab lossis tag nrho, cov kab mob inflammatory tau nce mus rau qee yam. Txoj kev tshawb no los ntawm Tonelli et al. pom tau tias qee qhov inflammatory biomarkers, xws li CRP, kuj tuaj yeem cuam tshuam qhov kev loj hlob ntawm CKD [5]. Cov kev tshawb fawb yav dhau los tau pom tias kev tiv thaiv kab mob hauv nruab nrog cev thiab cov kab mob interstitial tom qab tshwm sim vim yog mob tom qab AKI.
Nyob rau hauv vivo, nyob rau theem mob ntawm mob tubular necrosis (ATN), neutrophils tuaj yeem nkag mus sai sai, thiab cov monocytes thiab lymphocytes tsiv mus ntxiv, nws thiaj li ua rau kev loj hlob sai ntawm fibrosis [4]. Txawm li cas los xij, cov txheej txheem tshwj xeeb ntawm kev mob yog qhov nyuaj thiab yuav tsum tau kawm ntxiv.
kev hloov pauv ntawm epigenetic
Epigenetics xa mus rau cov kev hloov pauv ntawm cov noob caj noob ces los ntawm kev hloov pauv tom qab kev hloov pauv ntawm cov protein complexes yam tsis hloov pauv cov caj ces DNA sib lawv liag. Thaum lub sij hawm kev loj hlob ntawm AKI mus rau CKD, cov kev hloov pauv hauv epigenetic xws li DNA methylation, histone acetylation, thiab tsis-coding RNA qhia tsis tuaj yeem tsis quav ntsej [4]. Epigenetic kev hloov pauv uas tshwm sim tom qab lub raum ischemic raug mob tuaj yeem mob siab rau, koom nrog kev hloov pauv ntawm cellular rau qhov chaw huab cua xws li oxidative kev nyuaj siab, hypoxia, thiab mitochondrial puas tsuaj, thiab pab txhawb kev loj hlob ntawm cov mob ntev, fibrosis, thiab CKD [6].
nyob rau hauv xaus
Hauv kev xaus, maladaptation tom qab AKI yog ze ze rau qhov kev loj hlob thiab kev cia siab ntev ntawm CKD. AKI nws tus kheej yog tus txheej txheem kho tus kheej, tab sis tseem muaj peev xwm kho qhov tsis zoo. Cov kev tshawb fawb yav dhau los tau pom tias cov kev cuam tshuam rau cov txheej txheem cuam tshuam tuaj yeem txo qis fibrosis tom qab AKI thiab inhibit qhov kev loj hlob ntawm CKD. Txawm li cas los xij, tseem muaj qee qhov teeb meem thiab cov txheej txheem zoo tshiab hauv cov txheej txheem los ntawm AKI mus rau CKD uas yuav tsum tau tshawb nrhiav ntxiv los nrhiav cov hom phiaj kho mob tshiab thiab muab cov tswv yim tshiab rau kev kho mob.
Cov ntaub ntawv
1. Turgut F, et al. J Clin Med 2023,12(1):375.
2. Jiang M., et al. Am J Physiol Raum Physiol 2020,319(6): F1105-F1116?
3. Xu Xu, et al. Lub mechanism ntawm kev loj hlob ntawm mob raum raug mob rau mob raum kab mob. Phau ntawv Journal of Nephrology thiab Dialysis thiab raum Transplantation 2023,32(1):74-78.
4. Wang Z, et al. Int J Mol Sci 2022,23(18):10880.
5. Basile DP, et al. J. Am. Soc. Nephrol 2016, 27:687–697.
6. Tanemoto F, et al. Pem Hauv Ntej Mol Biosci 2022, 9: 1003227.
