本文選題：SC79 + 視網(wǎng)膜色素上皮(RPE)細(xì)胞��； 參考：《南京醫(yī)科大學(xué)》2017年博士論文

【摘要】：研究目的:過(guò)度的紫外線導(dǎo)致視網(wǎng)膜色素上皮氧化應(yīng)激和細(xì)胞凋亡。我們研究視網(wǎng)膜色素上皮細(xì)胞中,新型Akt激動(dòng)劑SC79抗紫外線(UV)氧化損傷作用,重點(diǎn)解析其相關(guān)分子機(jī)制。研究方法:為檢測(cè)SC79對(duì)UV引起的RPE細(xì)胞的保護(hù)作用,我們使用MTT、臺(tái)盼藍(lán)染色檢測(cè)細(xì)胞活性;流式細(xì)胞儀、組蛋白DNAELISA、Caspase-9活性以及線粒體去極化檢測(cè)等方法檢測(cè)細(xì)胞凋亡。我們使用Western blot檢測(cè)SC79活化RPE細(xì)胞中的Akt水平。通過(guò)Akt抑制劑MK-2206、shRNA沉默Aktl基因,分析Akt信號(hào)通路機(jī)制;通過(guò)qRT-PCR檢測(cè)RPE細(xì)胞中HO-1、NQO1、Nrf2變化的影響,以及Nrf2shRNA、顯性負(fù)性突變的Nrf2(DN,S40T)對(duì)SC79保護(hù)作用的影響,分析Nrf2信號(hào)通路機(jī)制。小鼠玻璃體腔注射SC79,通過(guò)視覺(jué)電生理檢測(cè)其對(duì)視網(wǎng)膜光損傷的保護(hù)作用。研究結(jié)果:SC79保護(hù)RPE細(xì)胞免受UV損害。SC79激活A(yù)kt,抑制UV引起的RPE細(xì)胞損傷;SC79活化Akt下游Nrf2信號(hào),保護(hù)RPE細(xì)胞免受UV誘導(dǎo)氧化損傷。SC79玻璃體腔內(nèi)注射減輕小鼠視網(wǎng)膜光損害。結(jié)論:SC79激活RPE細(xì)胞Akt-Nrf2信號(hào)通路,抑制UV氧化損傷。
[Abstract]:Objective: excessive ultraviolet radiation induced oxidative stress and apoptosis of retinal pigment epithelium.We studied the effects of a novel Akt agonist, SC79, on the oxidative damage of retinal pigment epithelial cells (RPE), focusing on its molecular mechanisms.Methods: in order to detect the protective effect of SC79 on UV-induced RPE cells, we used MTTand Trypan blue staining to detect cell activity, flow cytometry, histone DNA ELISA-Caspase-9 activity and mitochondrial depolarization to detect apoptosis.We used Western blot to detect the level of Akt in RPE cells activated by SC79.The mechanism of Akt signaling pathway was analyzed by Akt inhibitor MK-2206 siRNA silencing Aktl gene, and the changes of HO-1NQO1Nrf2 in RPE cells were detected by qRT-PCR, and the protective effect of Nrf2shRNAand Nrf2DNN S40T on SC79 was analyzed, and the mechanism of Nrf2 signaling pathway was analyzed.SC79 was injected into the vitreous cavity of mice and the protective effect of SC79 on retinal light injury was detected by visual electrophysiology.Results RPE cells were protected from UV damage. SC79 activated Akt.SC79 inhibited UV-induced injury of RPE cells and activated downstream Nrf2 signal of Akt. It also protected RPE cells from UV-induced oxidative damage. SC79 intravitreal injection alleviated retinal light damage in mice.Conclusion the Akt-Nrf2 signaling pathway of RPE cells was activated by WSC79 and UV oxidative damage was inhibited.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R774

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本文編號(hào)：1769634