突触融合蛋白17改善Aβ31-35诱导的小鼠海马神经细胞死亡  

STX17 improves Aβ31-35 induced death of hippocampal neurons in mice

作　　者：王宁[1] 周秀雅 何星鸿 张立飞 李朋佳 师姝 王丽[1,2] 王晓晖[1,2] WANG Ning;ZHOU Xiuya;HE Xinghong;ZHANG Lifei;LI Pengjia;SHI Shu;WANG Li;WANG Xiaohui(Department of Pathology,School of Basic Medicine,Shanxi Medical University,Taiyuan,Shanxi Province,030001,China;Basic Medical Research Center,School of Basic Medicine,Shanxi Medical University,Taiyuan,Shanxi Province,030001,China)

机构地区：[1]山西医科大学基础医学院病理教研室,太原030001 [2]山西医科大学基础医学院基础医学研究中心,太原030001

出　　处：《陆军军医大学学报》2022年第17期1712-1719,共8页Journal of Army Medical University

基　　金：山西省应用基础研究计划面上自然基金项目(201901D111197);山西省高等学校优秀成果(科学技术)培育项目(2020KJ012);山西省“1331工程”项目重点学科建设计划优势特色学科(1331KSC);山西省省筹资金资助回国留学人员科研项目(2020-082)。

摘　　要：目的探究突触融合蛋白17(syntaxin17,STX17)在Aβ诱导的小鼠海马神经细胞死亡中的作用。方法基于WGCNA方法选取与阿尔茨海默病显著相关的基因,与自噬基因库和SNARE家族基因取交集筛选关键基因;C57BL/6小鼠海马组织中注射浓度为1 g/L的Aβ31-35和使用终浓度为5μmol/L Aβ31-35处理HT22海马神经细胞,采用Western Blot检测STX17、LC3Ⅱ、P62的蛋白表达情况;CCK-8法检测Aβ31-35处理的HT22海马神经细胞存活率;慢病毒介导HT22海马神经细胞STX17过表达后,Western blot检测Aβ31-35处理后LC3Ⅱ、P62的蛋白表达情况。结果与阿尔茨海默病显著相关的Salmon和Black模块分别与自噬基因库和SNARE亚家族取交集获取关键基因STX17。与对照组比较,经Aβ31-35处理后,HT22细胞细胞存活率[(81.81±11.65)%]明显下降(P<0.05),小鼠海马组织和HT22细胞中STX17蛋白表达均显著降低(P<0.05),LC3Ⅱ和P62蛋白表达均显著升高(P<0.05);慢病毒介导HT22海马神经细胞STX17过表达后,显著逆转Aβ31-35诱导的LC3Ⅱ、P62的蛋白表达上调(P<0.05),并改善Aβ31-35诱导的HT22海马神经细胞存活率下降[(101.91±13.81)%vs(79.21±8.75)%,P<0.05]。结论STX17通过促进自噬来改善Aβ诱导的小鼠海马神经细胞死亡。Objective To explore the role of STX17 protein in Aβ-induced death of mouse hippocampal neuronal cells.Methods Based on Weighted correlation network analysis(WGCNA),the modules significantly related to Alzheimer’s disease(AD)were selected,and key genes were screened for cross-fertilization with autophagy gene bank and SNARE family genes.Aβ31-35 at a concentration of 1 g/L was used to inject the C57 BL/6 mouse hippocampal tissue,and HT22 hippocampal neuronal cells were treated with 5μmol/L Aβ31-35.Then the protein expression of STX17,LC3Ⅱand P62 was detected by Western blotting.The survival rate of the HT22 hippocampal neuronal cells treated by using Aβ31-35 was detected by CCK-8 assay.Protein expression of LC3Ⅱand P62 were determined by Western blotting after overexpression STX17 in HT22 hippocampal neuronal cells.Results The Salmon and Black modules significantly associated with AD crossed with autophagic gene pool and SNARE subfamily intersection STX17,respectively.Under the action of Aβ31-35 mouse hippocampal tissue and mouse HT22 hippocampal neuronal cells,and the survival rate of HT22 cells[(81.81±11.65)%vs(100.00±12.89)%,P<0.05]were decreased significantly,and the expression of STX17 was significantly reduced in both tissue and cells(P<0.05).The expression of tissue LC3Ⅱand P62 proteins were significantly elevated in the tissue(P<0.05),and in the cells(P<0.05).After lentivirus-mediated overexpression of STX17 in HT22 hippocampal neuronal cells,the protein expression upregulation of LC3 II and P62 induced by Aβ31-35 was significantly reversed,and the survival rate was improved in Aβ31-35-induced HT22 hippocampal neuronal cells[(101.91±13.81)%vs(79.21±8.75)%,P<0.05].Conclusion STX17 improves Aβ-induced death of mouse hippocampal neuronal cells by promoting autophagy.

关 键 词：STX17 AΒ 小鼠海马神经细胞 细胞死亡 自噬 

分 类 号：R338.26[医药卫生—人体生理学] R341[医药卫生—基础医学] R394.2