(Ib Ntu I) Kev Pom Zoo Pharmacological Muaj Peev Xwm Ntawm Resveratrol hauv Kev Txom Nyem Raum Laus
Mar 23, 2022
Abstract:Kev laus yog ib feem ntawm lub neej uas tsis muaj kev zam. Thaum peb laus zuj zus lawm, peb yuav muaj ntau yam teeb meem thiab kev puas tsuaj rau lub cev tseem ceeb, suav nroglub raum. Cov tshuaj uas twb muaj lawm raukab mob raumfeem ntau yog cov khoom siv hluavtaws; Yog li ntawd, cov khoom siv ntuj tsim nrog cov kev mob tshwm sim tsawg heev tau nyiam kev txaus siab los ntawm cov zej zog kev tshawb fawb thiab cov tuam txhab tshuaj. Kev tshawb nrhiav cov ntaub ntawv tau ua los sau cov ntaub ntawv tshawb fawb txog kev cuam tshuam ntawm resveratrol raulub raum laus. Tsis ntev los no, resveratrol tau tshwm sim los ua tus neeg sawv cev tiv thaiv kev laus. Qhov no ntau yam polyphenol exerts nws los tiv thaiv kev laus los ntawm kev cuam tshuam nyob rau hauv ntau yam pathologies thiab multi-signaling systems, xws li sirtuin hom 1, AMP-activated protein kinase, thiab nuclear factor-κB. Cov kws tshawb fawb tab tom sim txheeb xyuas cov txheej txheem ntxaws ntxaws thiab muaj peev xwm ua tau resveratrol-mediated interventions hauv txoj kev sib txawv ntawm qib molecular. Qhov kev tshuaj xyuas no qhia txog (i) cov laj thawj ua rau muaj feem cuam tshuam rau hauvlub raum lausthiab cov kev kho mob ntawm resveratrol, thiab (ii) qhov ua tau zoo ntawm resveratrol hauv kev ncua kev laus ntawm cov tshuajraumthaum txo tag nrho cov kev mob tshwm sim.
Ntsiab lus:antioxidant; anti-aging; AKI; CKD; lub raum laus; resveratrol; raum
CISTANCHE yuav txhim kho rau lub raum/ raum mob
Taw qhiaCov neeg laus yog nthuav dav thoob ntiaj teb [1]. Tsis ntev los no, kev laus noj qab nyob zoo tau raug suav tias yog qhov teeb meem tseem ceeb vim tias cov neeg laus nce ntxiv. Kev pheej hmoo ntawmmob raumntawm cov neeg laus tau nce.Lub raumkev laus yog txuam nrog cov hnub nyoog ntsig txog kev sib txuam. Thaum cov ncauj lus kom ntxaws molecular mechanism hauv qab lub raum laus tseem tsis tau paub, mobmob raum(AKI) thiab mob ntevmob raum(CKD) qhia ntau yam zoo sib xws nrog kev laus, suav nrog cellular senescence, o, fifibrosis, vascular rarefaction, poob ntawm glomeruli, thiab tubular dysfunction [2,3]. Kev cuam tshuam ntawm lub voj voog ntawm tes ua rau cov ntaub so ntswg senescent hauv ntau lub cev, suav nrograum,nrog lub hnub nyoog nce qib [4]. Kev hloov pauv ruaj khov ntawm lub raum qauv thiab nws txoj haujlwm hauv cov neeg laus pom qhov txo qis ntawm cov glomeruli (lub luag haujlwm rau nephrosclerosis), cortical ntim, glomerular filtration rate (GFR), thiab manifold raum cysts [3,5,6]. Kev laus ntxov ntxov thiab kev tuag siab yog exacerbated los ntawm o ua rau ntau lub cev tsis ua haujlwm lossis kab mob [7]. Yog li, cov txheej txheem cuam tshuam nrog rau cov kab mob hauv lub raum tuaj yeem pab nkag siab txog cov txheej txheem molecular koom nroglub raum laus. Nyob rau tib lub sij hawm, ib qho kev cog lus kho mob yuav tsum tau ceev kom normalize lub hnub nyoog uas muaj feem xyuam nrog cov teeb meem, nrog rau lub raum laus [3]. Resveratrol (3,40 ,5-trihydroxy-trans-stilbene), muaj ntau yam phenolic compound muaj nyob rau hauv ntau yam txiv hmab txiv ntoo, tshwj xeeb tshaj yog liab txiv hmab txiv ntoo thiab zaub, muaj peev xwm tiv thaiv kev laus thiab li no muaj peev xwm txhawb lub neej ncua los ntawm kev hloov kho ntawm cov cim tseem ceeb. Kev laus, piv txwv li, o, oxidative kev nyuaj siab, thiab fifibrosis, angiotensin II (Ang II), cell senescence, telomere attrition, mitochondrial dysfunction, angiogenesis, thiab platelet aggregation [8-11]. Resveratrol nyiam txwv cov hlwb los ntawm kev laus thiab inhibits senescence-associated secretory phenotype txoj kev loj hlob [12]. Calorie txwv (CR) thiab resveratrol muaj cov khoom zoo sib xws los tiv thaiv kev laus los ntawm kev ncua lub neej [13]. Tsis tas li ntawd, hauv cov qauv cellular senescence ntawm IMR-90 hlwb, 10 µM ntawm resveratrol zoo dua txo cov cellular senescence thiab apoptosis dua li CR [13]. Cov kev tshawb pom no qhia tias resveratrol tuaj yeem yog lwm txoj kev kho kev laus. Tsis tas li ntawd, ntau dua 244 qhov kev sim tshuaj, nrog rau 27 qhov kev sim tsis tu ncua, tau tshawb xyuas kev nyab xeeb thiab kev ua tau zoo ntawm resveratrol nrog rau nws cov haujlwm pleiotropic. Nws tau tshaj tawm tias muaj kev nyab xeeb txog li 5 g / hnub koob tshuaj thiab qhia tau tias muaj peev xwm tiv thaiv ntau yam qog noj ntshav, ntshav qab zib, rog rog, ntshav siab, kab mob plawv, kab mob raum, kab mob inflammatory, Alzheimer's disease, thiab lwm yam [14–16]. Nihei thiab cov npoj yaig tau tshaj tawm tias kev kho qhov ncauj resveratrol txhim kho qhov chaw kho mob ntawm nephrotic syndrome, suav nrog proteinuria thiab hypoalbuminemia, thiab normalized dyslipidemia hauv nas [17]. Resveratrol tau pom tias txo qis AKI los ntawm kev tswj hwm cov tshuaj tiv thaiv antioxidant thiab tiv thaiv kab mob hauv nas [18,19]. Tsis ntev los no, cov txiaj ntsig kev noj qab haus huv ntawm resveratrol rau kev kho ntau yam kab mob raum tau raug tshuaj xyuas [20–22]. Xav txog nws cov peev xwm pharmacological thoob plaws hauv lub cev thiab ntau yam mob, ntawm no peb tsuas yog tham txog qhov kev cia siab ntawm resveratrol hauv kev kho mob ntawm lub raum kev laus thiab nws cov kab mob sib txawv.
2. Cov txheej txheemKev tshawb nrhiav cov ntaub ntawv tau ua los sau cov ntaub ntawv tshawb fawb txog kev cuam tshuam ntawm resveratrol rauraumKev laus los ntawm cov ntaub ntawv muaj nyob hauv online, xws li PubMed, Google Scholar, thiab Scopus, siv cov ntsiab lus 'resveratrol ntawm cov kab mob hauv lub raum' thiab resveratrol ntawm cov txheej txheem kev laus hauv lub cev.raumxws li telomere shortening, DNA puas, cellular senescence mitochondrial puas, endoplasmic reticulum stress (ER stress), autophagy dysfunction oxidative stress, o, fibrosis, lifespan ex-tension, calorie txwv, thiab epigenetic modulation '. Txhua daim duab tau tsim los siv BioRender.com ( nkag mus rau 31 Lub Xya Hli 2021).
3. Pharmacological teebmeem ntawm Resveratrol rau cov kab mob raumCov neeg mob uas muaj keeb kwm ntawm AKI tuaj yeem txhim kho CKD [23]. CKD yog tus cwj pwm los ntawm kev puas tsuaj mitochondrial, ER kev nyuaj siab, autophagy dysfunction, oxidative stress, o, thiab fibrosis. Cov kev tiv thaiv ntawm resveratrol rau ntau yam kab mob hauv lub raum, xws li AKI thiab CKD, hauv vitro thiab hauv vivo tau tshaj tawm [20] thiab tam sim no tau sau tseg hauv qab no.
3.1.Kev mob raum mobAKI yog ib hom kab mob raum uas feem ntau cuam tshuam nrog kev tuag ntau ntxiv [24,25]. Txo glomerular muaj nuj nqi thiab tso zis tso zis yog thawj cov cim qhia ntawm AKI [26]. Qhov hnyav ntawm tus kab mob no tuaj yeem kwv yees los ntawm kev tshawb fawb pom tias feem pua ntawm cov neeg muaj kev txaus ntshai heev (16.9 feem pua rau 31. 0 feem pua ntawm cov tebchaws nyob sab hnub poob) raug mob los ntawm tus mob no [27].
CISTANCHE yuav txhim kho lub raum / raum mob ntshav qab zib
Ntau cov kev tshawb fawb tau pom tias cov tebchaw, xws li resveratrol, tuaj yeem muab ntau hom kev kho mob rau peb los tiv thaiv ntau yam uas cuam tshuam rau cov kab mob sib txawv [28,29].Hauv tib neeg, resveratrol tau ua pov thawj nws lub zog tiv thaiv AKI los ntawm inhibiting. Kev tsim cov pa oxygen reactive (ROS) [30]. Resveratrol-loaded nanoparticles tuaj yeem tiv thaiv ischemia / reperfusion (I / R)-vim lub raum raug mob hauv tus qauv nas [31]. Lwm txoj kev tshawb fawb ntawm luav tau pom tias resveratrol txo qisraumhypoxia, mitochondrial dysfunction, thiab raum tubular cell apoptosis [32]. Resveratrol kuj tau pom tias yog ib tus neeg sawv cev zoo los txo qis cov qog necrosis factor- (TNF-&x), interleukin (IL)-1 , thiabmob raummolecule (KIM)-1 expression in AKI [33]. Resveratrol tuaj yeem txo qhov kev tuag ntawm cov nas septic thiab alleviates AKI los ntawm kev txo ER kev ntxhov siab, inhibiting NF-κB txoj hauv kev ua kom, thiab txo cov lus teb inflammatory [34]. Tag nrho cov kev tshawb fawb no qhia tias resveratrol tuaj yeem yog tus neeg sawv cev muaj peev xwm los tawm tsam AKI. Ib qho kev tshawb fawb hauv vitro tau pom tias resveratrol tau pom tias yuav ua rau muaj zog ntawm tes thaum txo cov phosphorylation ntawm nuclear factor-κB (NF-κB) thiab tsim cov inflammatory yam tseem ceeb teb rau lipopolysaccharide (LPS), thiab txo kev puas tsuaj rau tunicamycin-induced tib neeg lub raum 2. (HK-2) hlwb los ntawm inhibiting inositol-requiring enzyme 1 (IRE1) ua kom [35]. Thaum resveratrol txo cadmium-induced mitochondrial ROS thiab apoptosis, nws nce mitochondrial biogenesis nrog rau cov cell viability hauv TCMK{14}} raum epithelial hlwb [36]. Tsis tas li ntawd, resveratrol txo qis ochratoxin A (ib nephrotoxin)-induced intracellular ROS ntau lawm thiab cellular puas nyob rau hauv HEK293 hlwb [37]. Txawm li cas los xij, kev tshawb xyuas ntxaws ntxaws yuav tsum tau piav qhia meej txog cov txheej txheem ntawm resveratrol hauv AKI.
3.2. CIromic raum Kab MobCKD paub tias hloov pauv cov haujlwm tsis tu ncua thiab cov qauv ntawm lub raum, feem ntau yog hloov tsis tau [38]. Ntau yam mob, xws li ntshav qab zib, kub siab, proteinuria, txo cov cytokine clearance, thiab cov kab mob ntev, yog cov feem ntau pheej hmoo rau CKD[39-4l]. Resveratrol tau pom tias yuav ua rau kom cov leeg ntiv nplhaib-ntiv tes 1 (MuRF1) thiab inhibit phosphorylation ntawm NF-xB hauv vivo qauv ntawm CKD[42]. Muaj kev sib txuas ntawm mitochondrial dysfunction thiab CKD pathogenesis. Resveratrol tau pom tias ua lub luag haujlwm tseem ceeb hauv kev rov qab los ntawm CKD los ntawm kev txhim kho mitochondrial kev ua haujlwm los ntawm kev ua haujlwm uas cuam tshuam nrog kev khaws cia ntawm mitochondrial membrane tej zaum yuav poob, txhim kho qib ATP, txo ROS tiam, thiab pab txhawb oxidative phosphorylation hauv nephrectomized nas I3]. Resveratrol nanoparticles tuaj yeem yog tus neeg sib tw zoo dua rau kev tiv thaiv CKD los ntawm kev txo qis ntawm NLR tsev neeg pyrin domain uas muaj 3 (NLRP3) inflammasome [44].
Cov tib neeg raug kev txom nyem los ntawm CKD tuaj yeem ntsib qhov txo qis ntawm kev tiv thaiv antioxidant vim txo qis kev noj cov vitamins thiab minerals, xws li vitamin C thiab selenium, Vim nws muaj peev xwm antioxidant, resveratrol muaj peev xwm tiv thaiv CKD[45A6]. Kev haus cawv dawb thiab roj txiv roj ua ke txo CKD plasma biomarkers, qhia txog qhov ua tau los tiv thaiv cov neeg mob CKD [47]. Ib txoj kev tshawb fawb tau tshaj tawm tias resveratrol tau txo qis qhov kev puas tsuaj rau lub raum tubular hauv unilateral ureteral obstruction-induced fibrotic nas [48]. Pterostilbene, ib qho analog ntawm resveratrol, tiv thaiv lub raum fibrosis thiab epithelial mus rau mesenchymal hloov (EMT) nyob rau hauv nas [A9].Tag nrho cov pov thawj no qhia tias resveratrol tuaj yeem ua tus neeg sawv cev tiv thaiv CKD.
Hauv HK-2 hlwb, resveratrol txo qis qabzib-induced oxidative kev nyuaj siab (xws li MDA thiab ROS qib) los ntawm kev nce superoxide dismutase (SOD) thiab catalase [50]. Tsis tas li ntawd, resveratrol txo qhov kev loj hlob ntawm kev hloov pauv- (TGF- )-vim EMT hauv HK-2 hlwb nyob rau hauv ib koob tshuaj [51]. Resveratrol txo qis cisplatin-induced cellular raug mob thiab apoptosis hauv nas proximal tubular hlwb [52. Resveratrol inhibited oxalate-induced inflammatory cytokines, colonization, thiab hyaluronan protein theem thaum nws nce ntau cov kev ua haujlwm antioxidant hauv tib neeg lub raum epithelial hlwb [53].
CISTANCHE yuav txhim kho lub raum / raum kab mob
Platelet-derived growth factor (PDGF) yog ib qho kev txhawb zog rau mesangial cell proliferation thiab koom nrog cov kab mob ntawm glomerulonephritis [54]. Kev kho mob ntawm mesangial hlwb nrog resveratrol inhibited PDGF-induced cell proliferation los ntawm kev tswj PI3K, Akt, ERK1/2, thiab c-Src [54]. Hauv podocytes, resveratrol txo qis cov piam thaj uas ua rau mitochondrial kev nyuaj siab, mitochondrial ROS ntau lawm, mitochondrial dysfunctions, thiab apoptosis [55] .Hauv HEK293cells, resveratrol txo qis cov piam thaj-induced aging markers, xws li -galactosidase 1, thaum nws nce ntxiv. ].Txawm li cas los xij, ntev (72 h) raug rau cov koob tshuaj siab (40-80 μM) ntawm resveratrol nce mitochondrial ROS, fibrotic, thiab apoptotic protein ntau ntau, thaum nws txo cov tshuaj tiv thaiv apoptotic thiab mitochondrial muaj nuj nqi hauv HK{{4} } cells [51]. Txij li cov qib ROS ntau dua ua rau ROS tawg ua rau mitochondrial puas [57], cov tshuaj resveratrol-induced siab ROS ntau ntau hauv mitochondria tuaj yeem ua rau muaj kev puas tsuaj mitochondrial hauv cov hlwb. Tsis tas li ntawd, resveratrol ntawm cov koob tshuaj siab (50–75 µM) nce NF-κB-mediated inflammatory teebmeem hauv IL-1 lossis TNF- - kho mesangial hlwb thiab lub raum proximal tubular LLCPK1 hlwb [58]. Txawm li cas los xij, xav txog cov koob tshuaj tseem ceeb ntawm resveratrol los ua kom muaj kev tiv thaiv los yog cytotoxic, kev tshawb fawb tseem ceeb yuav tsum tau txiav txim siab txog qhov teeb meem tshwm sim los ntawm kev kho resveratrol thiab pom zoo rau kev siv tshuaj kho mob.
4. Pharmacological teebmeem ntawm Resveratrol rau Kev Laus Biomarkers nyob rau hauv lub raumResveratrol muaj ntau yam txiaj ntsig hauv ntau lub cev, suav nrog lub hlwb, daim siab, lub plawv, lub ntsws, thiab txiav txiav, hais txog kev tiv thaiv kev laus [14-16](s qhia hauv Table]). Nws kuj muaj ntau yam kev tiv thaiv kev laus hauv lub raum [20-22](s qhia hauv Table2). Cov khoom tiv thaiv kev laus ntawm resveratrol tau raug tshuaj xyuas [59]. Ib lub cev loj hlob ntawm cov pov thawj qhia tias resveratrol siv nws txoj kev tiv thaiv rau lub raum kev laus los ntawm kev tswj cov renin-angiotensin system (RAS) thiab alleviating o, oxidative kev nyuaj siab, thiab ællular senescence J10,1ll. Kev noj qab haus huv cov txiaj ntsig ntawm resveratrol ntawm lub raum epithelial hlwb, lub raum corpuscle, raum fibroblasts, thiab raum mob qog noj ntshav, txawm nyob rau theem molecular, ob qho tib si hauv vivo thiab hauv vitro, tau tshaj tawm [20]. Cov tshuaj muaj peev xwm ntawm resveratrol tiv thaiv qee yam plausible (xws li telomere shortening, cellular senescence los ntawm DNA puas, mitochondrial dysfunction, ER kev nyuaj siab, thiab autophagy dysfunction oxidative kev nyuaj siab, o, thiab fibrosis, raws li qhia nyob rau hauv daim duab 1) lub luag hauj lwm rau lub raum laus yog delineated. nyob rau hauv seem no.
4.1. Telomere ShorteningThe 6-bp recurred sequence, TTAGGG, which is known as the telomere, constructs the end of each mammal's chromosome. Mitotic cell division is a fundamental process, and during each cycle of division, almost 50-200 bp telomeric sequences tend to be eroded due to the"end replication problem", causing telomere shortening [89, The mechanism of limiting transcription by DNA polymerase is associated with replicative senescence, apoptosis, cancer, and CKD [90,91]. Thus, the telomeric length is considered to be a probable biomarker of kidney aging [92]. The most consolidated telomerase function having unlimited replicative dynamics is demonstrated in human cancers[91,93]. Telomeric shortening is ultimately responsible for significant changes in the kidney, such as decreases in GFR, urinary concentration, urinary acidification, kidney mass, and blood flow [o4.951. A critically short telomere evokes cell-cycle inhibitor p21 and CDKIs, which play a crucial role in arresting the cell cycle progression, resulting in apoptosis of kidney cells [96,97]. An inhibitory protein named p16INK4a is responsible for inhibiting the activity of CDK4 and CDK6 [96]. The manifestations of p21 and p16INK4a become exacerbated by activation of p53, with serious impacts on vital organs, such as the kidneys, in the elderly population [98]. The propensity to shortening of the telomeres is commensurate to kidney aging, along with aging in most other organs, tissues, and cells, including the lung, pancreas, liver, muscle, hepatocytes, intestinal epithelial cells, peripheral blood cells, lymphocytes, and vascular endothelial cells [99,100]. Telomerase is a reverse transcriptase enzyme (TERT)that adds repetitive sequences to telomeres in dividing cells to prevent the telomeres from shorteningJ101]. In CKD patients, the lowest levels of telomerase activity (TLMA) and TERT expression were detected, while they had the highest IL-6 and C-reactive protein (CRP) levels [102]. Resveratrol activates telomerase activity in epithelial [103] and endothelial progenitor cells [104]. Direct modulation of p53 by resveratrol has also been observed [52]. Resveratrol treatment promoted p53 deacetylation and thereby attenuated cisplatin-induced kidney apoptosis and improved the GFR [52]. However, in cancer, most cancer cells with limitless proliferative capacity protect their telomeres by expressing high TLMA. Resveratrol at higher concentrations (>2.5 ug / mL) ua rau muaj kev cuam tshuam loj heev thiab muaj zog-dependent downregulation ntawm TLMA hauv carcinoma cell kab, nrog 100 feem pua inhibition ntawm 40 ug / mL 【105. Tsis tas li ntawd, resveratrol kuj tau pom tias muaj txiaj ntsig zoo hauv kev txo qis kev qhia ntawm h-TERT protein hauv tib neeg A431 epidermoid carcinoma hlwb [106].
4.2. Cellular Senescence thiab DNA puasAberrant tsub zuj zuj ntawm cov kab mob senescent nyob rau hauv cov lus teb rau lub sij hawm signaling txhawb lub raum kab mob kuj yog txuam nrog rau lub hnub nyoog txog kev poob ntawm lub raum ua hauj lwm [107]. Cellular senescence yog ib lub xeev uas cellular sib txawv thiab proliferation yog inhibited. DNA kev puas tsuaj yog ib tug ubiquitous mediator rau ob replicate superannuation uas yog coj los ntawm ntxov ntxov cellular senescence thiab telomere shortening induced los ntawm ntau yam pathogenic yam, xws li oxidative kev nyuaj siab, kev hloov, thiab tsis ua hauj lwm ntawm DNA kho mechanisms [108]. Hauv lub raum, ob qho tib si G1- thiab G2- ntes cov hlwb senescent txuam nrog cov hnub nyoog nce qib thiab kab mob raum []. Ib qho kev pheej hmoo DNA puas teb (DDR) cov cim qhia tau muab los ntawm cov hlwb senescent los ua rau lub hom phiaj raug ntes. Kev ua kom DDR cuam tshuam rau cov chromatin ntawm DNA puas thiab tag nrho cov genome ib yam nkaus [109], Ntxiv mus, cov kab mob ntawm atherosclerosis yuav exacerbated los ntawm interferon-gamma (IFN- ), uas entails txhawb cov cellular senescence sai tom qab lub triggering ntawm ap. 53-kab mob DNA puas tsuaj [110]. Oxidative kev nyuaj siab ua raws li ib tug catalyst nyob rau hauv lub cellular senescence txheej txheem, thiab qhov teeb meem no ua rau lub raum puas, uas nws thiaj li hloov mus rau lub raum laus.
Sepsis yog ib lub xeev ntawm kev cuam tshuam inflammatory homeostasis ua rau ntau lub cev tsis ua hauj lwm, qhov twg resveratrol kev kho mob yog npaj los txo oxidative DNA puas [78.111] Resveratrol kev kho kom txo qis cov kev cai ntawm cov tswj kev koom nrog hauv lub voj voog ntawm tes thiab txoj hauv kev zoo [112]. Tsis tas li ntawd, kev kho resveratrol impedes siab-glucose-induced cell senescence (-galactosidase) hauv ob lub raum [113]. Kev tswj hwm ntawm Resveratrol tau ua rau muaj kev cuam tshuam ntawm cov neeg tswj hwm koom nrog hauv lub voj voog ntawm tes thiab txoj hauv kev senescence, xws li cyclin-dependent kinase (CDK4 thiab 6), cyclin D1, p21, thiab p16, ua rau muaj qhov tsis zoo ntawm apoptosis hauv plab hnyuv hauv vivo thiab hauv vitro [ 112] ib.
4.3. Mitochondrial puasMitochondria raug suav hais tias yog cov organelles muaj zog heev vim tias lawv muaj ntau yam haujlwm hauv lub cell [114]. Mitochondrial puas muaj feem cuam tshuam rau lub raum ua haujlwm. Txawm hais tias mitochondrial ROS plays lub luag haujlwm tiv thaiv mus txog rau ib theem, nws tuaj yeem ua rau mitochondrial tsis ua haujlwm thiab cellular puas tom qab dhau qhov txwv [115]. Qhov kev hloov pauv ntawm mitochondrial DNA (mtDNA) yog 10 mus rau 1000 npaug siab dua li ntawm chromosomal DNA.Ob leeg exogenous (UV, puag analog, ROS, thiab lwm yam) thiab endogenous stimuli (ib zaug lossis ob zaug kev puas tsuaj, tsis sib haum hauv hauv paus khub) tuaj yeem ua rau mtDNA puas[116]. Yog li, ib qho kev xaiv kho mob uas tuaj yeem txhim kho mitochondrial Fitness yog tsim nyog los kho cov kab mob raum [117].
Resveratrol khaws cia mitochondrial kev ncaj ncees thiab txhim kho autophagy los ntawm inhibition ntawm mitochondria kev puas tsuaj teeb liab zoo li NLRP3 inflammasome-derived IL-1 ntau lawm thiab pyroptosis hauv macrophages[84]. Resveratrol txhawb kev khiav tawm ntawm mtDNA los ntawm ROS los ntawm kev txo cov cellular H, O, thiab qib [118,119]. Resveratrol tsub kom qhov kev qhia ntawm cov proteins koom nrog hauv cov khoom siv hluav taws xob thauj khoom, cov ntsiab lus mitochondrial, thiab mitochondrial biogenesis markers [118]. Tsis tas li ntawd, resveratrol tau pom tias ua kom autophagy kom txo qis mitochondrial tsis ua haujlwm thiab apoptosis [73]. Kev tswj hwm ntawm resveratrol txhim kho mitochondrial kev ua haujlwm hauv ob lub raum los ntawm kev tswj hwm ntawm sirtuin hom 1 (SIRT1) thiab PGC-1 deacetylation, uas yog ib qho tseem ceeb tshaj plaws rau lub raum tiv thaiv mechanisms ntawm resveratrol [43].
4.4. ER Kev nyuaj siabLub luag haujlwm ntawm ER kev ntxhov siab yog tshwm sim rau ntau lub raum kab mob, suav nrog raum fibrosis, glomerulopathies, thawj glomerulonephritis, mob ntshav qab zib nephropathy, thiab lwm yam. Kev ntxhov siab ua rau apoptosis ntawm lub raum hlwb, ua rau lub raum puas [120-122]. Kev ntxhov siab nyob rau hnub so yog ib qho txiaj ntsig uas cuam tshuam nrog kev tsis txaus ntawm cov protein homeostasis thiab kev hloov pauv tom qab hloov pauv ntawm cov protein hauv lub raum uas ua rau ER kev nyuaj siab [123]. Txawm tias me ntsis txo qis autophagy los yog micro-autophagy accelerates o thiab ER kev ntxhov siab hauv cov ntaub so ntswg adipose nrog kev laus [124]. Cov txheej txheem cuam tshuam nrog ER kev ntxhov siab hauv lub raum yog cuam tshuam nrog kev sib txuas sib txuas / pas dej ua ke ntawm kev ntxhov siab ntawm kev sib txuas lus, qhov twg ntau yam tsis xws li oxidative stress, Akt pathway, thiab lipid thiab epigenetic alterations, ua rau lub raum raug kev nyuaj siab hypoxia [125. ]. Ntxiv mus, redox signaling mechanisms koom nrog hauv ROS cascade ua rau muaj kev ntxhov siab ntau ntxiv los ntawm ER kev ntxhov siab, uas tsis tsuas yog ua rau lub raum raug mob tab sis kuj ua rau muaj ntau yam teeb meem hauv tib neeg [126].
Nrhiav kev daws teeb meem, vim muaj kev txwv tsis pub siv txoj kev kho mob rau lub raum kab mob / kev laus, kev hloov pauv ntawm ER kev ntxhov siab siv cov tshuaj siv tshuaj yuav yog qhov kev xaiv zoo / txoj hauv kev [121,127]. Ntxiv rau qhov no, kev poob qis ntawm ER kev ntxhov siab-qhia cov proteins, piv txwv li, reticulon 1 (RTN1), tuaj yeem pab txhawb kom tsis txhob muaj kev ntxhov siab nrog rau kev txo qis hauv lub raum [128]. Ntxiv mus, resveratrol, raws li kev kho mob ntuj tsim, pom tau tias muaj txiaj ntsig zoo hauv kev txo ER kev ntxhov siab thiab yog li txhim kho lub raum kev ua haujlwm thiab tubular cell raug mob [35]. Resveratrol tau raug pov thawj los txo cov theem ntawm ER cov teeb meem ntsig txog kev ntxhov siab, uas nyob rau hauv lem attenuate urinary protein, ntshav qabzib, raum puas, thiab AKI nrog rau cov neeg tuag [34]. Resveratrol txawm tiv thaiv cadmium (Cd)-induced ER kev nyuaj siab thiab nephrotoxicity [129]. Tsis tas li ntawd, H, O2-induced ER kev nyuaj siab kuj yog alleviated los ntawm kev kho nrog resveratrol los ntawm kev txhim kho redox tshuav nyiaj li cas nyob rau hauv bovine mammary epithelial hlwb[130].
