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

【摘要】：研究目的:過度的紫外線導(dǎo)致視網(wǎng)膜色素上皮氧化應(yīng)激和細胞凋亡。我們研究視網(wǎng)膜色素上皮細胞中,新型Akt激動劑SC79抗紫外線(UV)氧化損傷作用,重點解析其相關(guān)分子機制。研究方法:為檢測SC79對UV引起的RPE細胞的保護作用,我們使用MTT、臺盼藍染色檢測細胞活性;流式細胞儀、組蛋白DNAELISA、Caspase-9活性以及線粒體去極化檢測等方法檢測細胞凋亡。我們使用Western blot檢測SC79活化RPE細胞中的Akt水平。通過Akt抑制劑MK-2206、shRNA沉默Aktl基因,分析Akt信號通路機制;通過qRT-PCR檢測RPE細胞中HO-1、NQO1、Nrf2變化的影響,以及Nrf2shRNA、顯性負性突變的Nrf2(DN,S40T)對SC79保護作用的影響,分析Nrf2信號通路機制。小鼠玻璃體腔注射SC79,通過視覺電生理檢測其對視網(wǎng)膜光損傷的保護作用。研究結(jié)果:SC79保護RPE細胞免受UV損害。SC79激活A(yù)kt,抑制UV引起的RPE細胞損傷;SC79活化Akt下游Nrf2信號,保護RPE細胞免受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細胞Akt-Nrf2信號通路,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)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R774

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