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  

THE ROLE OF UCH-L1 IN REGULATING α-SYNUCLEIN EXPRESSION IN THE HIPPOCAMPUS OF MICE AFTER ACUTE HYPOBARIC HYPOXIA EXPOSURE

作　　者：武磊[1] 田蕾[1] 赵博[2] 张志清[1] 李康[1] 杲修杰[1] 周学思[1] 刘晓华[1] 

机构地区：[1]军事医学科学院卫生学环境医学研究所,天津300050 [2]秦皇岛市海港医院

出　　处：《解放军预防医学杂志》2015年第6期604-607,共4页Journal of Preventive Medicine of Chinese People's Liberation Army

基　　金：国家自然科学基金项目(No.30800456;31470061);天津市应用基础与前沿技术研究计划项目(No.14JCZDJC32700;No.12JCYBJC15800)

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(P<0.05),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)(P<0.05),同时LC3Ⅱ/Ⅰ的比值也显著升高(P<0.05)。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。Objective To define the effects of UCH- LI gene knockout on the expression of α- synuclein in hippocampus of mice in acute hypobaric hypoxia conditions and its mechanisms,so as to provide the basis for maintaining brain function research.Methods Male and female UCH- L1 gene heterozygous mice（UCH- L1^＋/-）were selected for mating and obtaining UCH- L1 gene knockout homozygotes mice（UCH- L1^-/-） and wild-type mice（UCH- L1^＋/＋ The genotype of offspring was identified by PCR method.Then UCH- L1^＋/＋^ mice and UCH- L1^-/- mice were placed in a hypobaric chamber simulating altitude 8000 m above sea level for 8h to establish acute hypobaric hypoxia model.In order to evaluate the effects of UCH- L1 gene knockout on α- synuclein content and autophagy degradation pathway in mice hippocampus after acute hypobaric hypoxia exposure,protein expression changes of UCH- L1,α- synuclein and LC3 were assayed by western blot method.Results α- synuclein expression（1.31±0.096）in the hippocampus of wild-type mice after acute hypobaric hypoxiaexposure significantly increasedcompared with the control group（0.702±0.121）（P〈0.05）,and the ratio of LC3Ⅱ and Ⅰincreased mildly,but the expression of UCH- Llhad no change.When knockout UCH- L1 gene,α- synuclein in hippocampus（0.952 ±0.093） decreased significantly（P〈0.05） after acute hypobaric hypoxia exposure compared with the wild- type control group（1.490±0.074）,while the ratio of LC3 II and I also increased significantly（P〈0.05）.Conclusion UCH- L1 gene knockout can reduce the elevated levels of hippocampal α- synuclein induced by acute hypobaric hypoxia,and one of the mechanisms might due to promoting autophagy pathway activation.

关 键 词：泛素羧基端水解酶L1 低压低氧 Α-突触核蛋白 基因敲除 LC3蛋白 

分 类 号：R363[医药卫生—病理学]