本文關鍵詞： PTEN 視網(wǎng)膜脫離 光感受器細胞 凋亡 PI3K/Akt信號通路　出處：《上海交通大學》2015年博士論文　論文類型：學位論文

【摘要】：目的:視網(wǎng)膜脫離后光感受器細胞的凋亡是視功能恢復不良的的主要原因。PTEN是神經(jīng)元凋亡發(fā)生中關鍵的調節(jié)因素。PTEN/PI3K/Akt信號通路作為一種細胞存活信號通路,其神經(jīng)保護作用已得到確認,而且它的作用靶點也逐漸得到確定。本課題采用PTEN的特異性抑制劑bp V(pic)干預,擬研究PTEN/PI3K/Akt信號通路及其下游分子以及光感受器細胞凋亡的變化特點,闡明PTEN/PI3K/Akt信號通路對視網(wǎng)膜脫離后光感受器細胞凋亡的調控機制。方法:建立視網(wǎng)膜脫離模型,成模后1 d、2 d、3 d和7 d運用Western Blot和免疫熒光檢測視網(wǎng)膜內PTEN表達的變化。建模后視網(wǎng)膜下注射bp V(pic),運用Western Blot和免疫熒光檢測p-Akt和Bcl-2在視網(wǎng)膜的表達與分布;運用Western Blot檢測視網(wǎng)膜內p-PDK1、p-BAD、胞漿Cyt c和Caspase-3蛋白水平的表達;ELISA檢測PIP3的表達水平;運用TUNEL檢測視網(wǎng)膜的細胞凋亡情況;記錄ONL的厚度。結果:視網(wǎng)膜脫離后PTEN的表達逐步上調,3 d為峰值(P0.05),之后逐漸下降,7 d時基本恢復到正常。視網(wǎng)膜下注射bp V(pic)后,能使視網(wǎng)膜脫離后光感受器細胞的凋亡顯著減少(P0.05),視網(wǎng)膜ONL厚度增加(P0.05)。與vehicle-treated RD組相比,bp V-treated RD組的p-Akt和p-PDK1顯著升高(P0.05)。此外,bp V還能使p-BAD和Bcl-2的表達上調(P0.05),胞漿Cyt c和Caspase-3的表達降低(P0.05)。結論:PTEN參與了視網(wǎng)膜脫離后光感受器細胞的凋亡過程。抑制PTEN可通過激活PI3K/Akt信號通路,抑制線粒體通路的活化,從而減少光感受器細胞凋亡的發(fā)生。
[Abstract]:Objective: apoptosis of photoreceptor cells after retinal detachment is the main cause of poor recovery of visual function. PTEN is a key regulatory factor in neuronal apoptosis. PTEN / PI3K / Akt signaling pathway is a cell survival signal pathway. Its neuroprotective effect has been confirmed, and its target has been gradually determined. In this study, the characteristics of apoptosis of PTEN/PI3K/Akt signaling pathway, its downstream molecules and photoreceptor cells were studied with the intervention of BP Vpica, a specific inhibitor of PTEN. To elucidate the mechanism of PTEN/PI3K/Akt signaling pathway regulating photoreceptor cell apoptosis after retinal detachment. Methods: retinal detachment model was established. The changes of PTEN expression in the retina were detected by Western Blot and immunofluorescence on the 3rd and 7th day after the model was established. The expression and distribution of p-Akt and Bcl-2 in the retina were detected by Western Blot and immunofluorescence, and the expression and distribution of p-Akt and Bcl-2 in the retina were detected by Western Blot and immunofluorescence. Western Blot was used to detect p-PDK1 p-BAD. the expression of cytoplasmic Cyt c and Caspase-3 protein was detected by Elisa, and TUNEL was used to detect the apoptosis of retina. The thickness of ONL was recorded. Results: after retinal detachment, the expression of PTEN was gradually up-regulated to a peak value of P0.05 at 3 days, then gradually decreased to normal at 7 days. Compared with vehicle-treated Rd group, p-Akt and p-PDK1 were significantly increased in p-Akt and p-PDK1 in vehicle-treated Rd group. In addition, BPV could also up-regulate the expression of p-BAD and Bcl-2, and increase the expression of p-BAD and Bcl-2 in the cytoplasm Cyt c. Conclusion Caspase-3 is involved in the apoptosis of photoreceptor cells after retinal detachment. Inhibition of PTEN may be mediated by activation of PI3K/Akt signaling pathway. Inhibition of mitochondrial pathway activation, thereby reducing photoreceptor cell apoptosis.
【學位授予單位】：上海交通大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R774.12

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