UCH-L1对急性低压低氧小鼠海马中α-突触核蛋白表达水平的调控作用

发布时间：2018-03-04 06:21

  本文选题：泛素羧基端水解酶L　切入点：低压低氧　出处：《解放军预防医学杂志》2015年06期 　论文类型：期刊论文

【摘要】：目的探讨急性低压低氧条件下UCH-L1基因敲除对小鼠海马中α-突触核蛋白(α-Syn)表达水平的影响及其机制,为治疗α-Syn蛋白相关的神经系统疾病提供依据。方法采用UCH-L1基因杂合子(UCH-L1~(+/-))小鼠雌雄交配的方式获得UCH-L1基因敲除纯合子(UCHL1~(-/-))小鼠和野生型小鼠(UCH-L1~(+/+)),PCR法鉴定小鼠的基因型。将UCH-L1~(+/+)小鼠和UCH-L1~(-/-)小鼠放入低压氧舱模拟海拔8000 m高度,持续低氧8 h,建立急性低压低氧模型。采用Western Blot法检测小鼠海马中UCH-L1、α-突触核蛋白及LC3蛋白表达水平的变化,观察UCH-L1基因敲除对α-突触核蛋白表达水平及其相关细胞自噬降解通路的影响。结果与对照组(0.702±0.121)相比,急性低压低氧可诱导野生型小鼠海马中α-突触核蛋白表达水平(1.310±0.096)显著升高(P0.05),LC3Ⅱ/Ⅰ的比值轻度升高,而对UCH-L1蛋白的表达水平没有影响。当敲除UCH-L1基因的小鼠经急性低压低氧处理后,小鼠海马中α-突触核蛋白表达水平(0.952±0.093)明显低于野生型对照组(1.490±0.074)(P0.05),同时LC3Ⅱ/Ⅰ的比值也显著升高(P0.05)。结论UCH-L1基因敲除降低了急性低压低氧诱导的α-突触核蛋白表达水平升高,其机制之一可能与小鼠在急性低压低氧时因敲除UCH-L1基因而进一步促进细胞自噬通路的活化有关。
[Abstract]:Objective to investigate the effect of UCH-L1 knockout on the expression of 伪 -synaptophysin (伪 -Sync) in hippocampus of mice under acute hypobaric hypoxia and its mechanism. In order to provide evidence for the treatment of 伪 -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, 伪 -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 伪 -synaptophysin and its related autophagy pathway, the results were compared with that of control group (0.702 卤0.121). Acute hypobaric hypoxia induced the expression of 伪 -synaptophysin in hippocampus of wild-type mice (1.310 卤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 伪 -synaptophysin in hippocampus of mice (0.952 卤0.093) was significantly lower than that of wild type control group (1.490 卤0.074), and the ratio of LC3 鈪，

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