本文選題：泛素羧基端水解酶L　切入點(diǎn)：低壓低氧　出處：《解放軍預(yù)防醫(yī)學(xué)雜志》2015年06期 　論文類型：期刊論文

【摘要】：目的探討急性低壓低氧條件下UCH-L1基因敲除對(duì)小鼠海馬中α-突觸核蛋白(α-Syn)表達(dá)水平的影響及其機(jī)制,為治療α-Syn蛋白相關(guān)的神經(jīng)系統(tǒng)疾病提供依據(jù)。方法采用UCH-L1基因雜合子(UCH-L1~(+/-))小鼠雌雄交配的方式獲得UCH-L1基因敲除純合子(UCHL1~(-/-))小鼠和野生型小鼠(UCH-L1~(+/+)),PCR法鑒定小鼠的基因型。將UCH-L1~(+/+)小鼠和UCH-L1~(-/-)小鼠放入低壓氧艙模擬海拔8000 m高度,持續(xù)低氧8 h,建立急性低壓低氧模型。采用Western Blot法檢測(cè)小鼠海馬中UCH-L1、α-突觸核蛋白及LC3蛋白表達(dá)水平的變化,觀察UCH-L1基因敲除對(duì)α-突觸核蛋白表達(dá)水平及其相關(guān)細(xì)胞自噬降解通路的影響。結(jié)果與對(duì)照組(0.702±0.121)相比,急性低壓低氧可誘導(dǎo)野生型小鼠海馬中α-突觸核蛋白表達(dá)水平(1.310±0.096)顯著升高(P0.05),LC3Ⅱ/Ⅰ的比值輕度升高,而對(duì)UCH-L1蛋白的表達(dá)水平?jīng)]有影響。當(dāng)敲除UCH-L1基因的小鼠經(jīng)急性低壓低氧處理后,小鼠海馬中α-突觸核蛋白表達(dá)水平(0.952±0.093)明顯低于野生型對(duì)照組(1.490±0.074)(P0.05),同時(shí)LC3Ⅱ/Ⅰ的比值也顯著升高(P0.05)。結(jié)論UCH-L1基因敲除降低了急性低壓低氧誘導(dǎo)的α-突觸核蛋白表達(dá)水平升高,其機(jī)制之一可能與小鼠在急性低壓低氧時(shí)因敲除UCH-L1基因而進(jìn)一步促進(jìn)細(xì)胞自噬通路的活化有關(guān)。
[Abstract]:Objective to investigate the effect of UCH-L1 knockout on the expression of 偽 -synaptophysin (偽 -Sync) in hippocampus of mice under acute hypobaric hypoxia and its mechanism. In order to provide evidence for the treatment of 偽 -Syn protein-related neurological diseases, UCH-L1 gene heterozygotes of UCH-L1 (/ -r-1) mice were used to obtain UCH-L1 gene knockout homozygotes (UCHL1) and wild type mice to identify the bases of UCH-L1 (/ PCR) mice. The UCH-L1 (/) mice and the UCH-L _ (1) / -r _ (-) mice were placed in a hypobaric oxygen chamber at a simulated altitude of 8000 m, Acute hypobaric hypoxia model was established after hypoxia for 8 h. The expression levels of UCH-L1, 偽 -synaptophysin and LC3 protein in hippocampus of mice were detected by Western Blot method. To observe the effect of UCH-L1 knockout on the expression of 偽 -synaptophysin and its related autophagy pathway, the results were compared with that of control group (0.702 鹵0.121). Acute hypobaric hypoxia induced the expression of 偽 -synaptophysin in hippocampus of wild-type mice (1.310 鹵0.096). But there was no effect on the expression of UCH-L1 protein. When the UCH-L1 gene knockout mice were treated with acute hypobaric hypoxia, The expression level of 偽 -synaptophysin in hippocampus of mice (0.952 鹵0.093) was significantly lower than that of wild type control group (1.490 鹵0.074), and the ratio of LC3 鈪，

本文編號(hào)：1564492