丁苯酞对慢性酒精中毒大鼠内质网应激相关基因的影响  

Bioinformatics analysis of butylphthalide intervention on differentially expressed genes in rats with chronic alcoholism

作　　者：董家行 姜万举 刘佳聪 朱甲婧 张占蕊 张瑞岭[2] 杜爱林[1,2] DONG Jia-Xing;JIANG Wan-Ju;LIU Jia-Cong(Department of Physiology and Neurobiology and Sino-UK Joint Laboratory for Brain Function and Injury,Henan Provincial Key Laboratory of Brain Research,Xinxiang Medical University,Xinxiang 453003,Henan,China)

机构地区：[1]新乡医学院生理学与神经生物学教研室,中英脑功能损伤联合实验室,河南省高校脑研究重点实验室培育基地,河南新乡453003 [2]新乡医学院第二附属医院,河南省生物精神病学重点实验室

出　　处：《中国老年学杂志》2020年第10期2147-2154,共8页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81471351);河南省教育厅课题(15A310006);河南省科技厅基础研究项目(142300410026);河南省科技发展计划国际科技合作项目(124300510035);河南省卫生科技创新型人才工程专项经费(3052);河南省高校科技创新团队(17IRTSTHN023);河南省医学教育研究课题(wjlx2018104);新乡医学院博士启动项目(2019)。

摘　　要：目的从基因水平探讨丁苯酞对慢性酒精中毒大鼠海马的影响及其治疗机制。方法借助基因芯片技术获取慢性酒精中毒模型组和用药组大鼠海马体的相关基因表达数据集,再利用生物信息学的分析方法对差异表达基因进行筛选与分析,采用实时荧光定量聚合酶链反应对关键mRNA的表达进行验证。此外,通过水迷宫检测慢性酒精中毒大鼠学习记忆的损伤。结果一共筛选出585个差异表达基因,其中320个表达上调,265个表达下调。其中涉及的主要信号通路有氧化磷酸化通路,黏合连接,蛋白酶体通路,脂肪细胞因子信号通路,丝裂原活化蛋白激酶(MAPK)信号转导通路,破骨细胞的分化,黏着,幽门螺杆菌感染中的上皮细胞信号转导,帕金森病通路,聚酮糖的生物合成等。结论通过生物信息学的分析发现,丁苯酞可以将由慢性酒精中毒造成差异表达的多个基因反向调控到正常水平,通过Sec61G、Ndufa4、Ndufa2等与内质网或线粒体相关基因的表达,缓解了内质网应激,减轻线粒体损伤,在一定程度上保护了神经元细胞。其中RPSA、RPS9、RPS11、SRP19、Sec61G、EIF3E、LARS、Ndufa4、Ndufb6、Ndufa2等基因编码的蛋白。Objective To explore the effects of butylphthalide on hippocampus in rats with chronic alcoholism and provide new ideas for the treatment of chronic alcoholism.Methods Gene expression data sets of hippocampus in rats with chronic alcoholism and rats treated with butylphthalide were obtained by gene chip technology,and then differentially expressed genes were screened and analyzed by bioinformatics analysis method.The expression of key mRNA was verified by real-time quantitative PCR(qPCR).In addition,water maze was used to detect learning and memory impairment in rats with chronic alcoholism.Results A total of 585 differentially expressed genes were screened out,of which 320 were up-regulated and 265 down regulated.The main signal pathways involved were oxidative phosphorylation,adherens junction,proteasome,adipocytokine signaling pathway,MAPK signaling pathway,osteoclast differentiation,epithelial cell signaling in Helicobacter pylori infection,Parkinson′s disease,polyketide sugar unit biosynthesis.Conclusions Through bioinformatics analysis,it is found that butylphthalide could reversely regulate the expression of multiple genes,which expressed differently after chronic alcoholism,to normal levels.By regulating the expression of SEC61G,NDUFA4,NDUFA2 and other genes related to endoplasmic reticulum or mitochondria,it might relieve endoplasmic reticulum stress and alleviate mitochondrial damage,and protect neuron cells to a certain extent.The proteins encoded by genes such as RPSA,RPS9,RPS11,SRP19,SEC61G,EIF3E,LARS,NDUFA4,NDUFB6,NDUFA2,are central proteins in the endoplasmic reticulum and mitochondria.The search for new drugs for chronic alcoholism will provide new directions.

关 键 词：慢性酒精中毒 丁苯酞 生物信息学 差异表达基因 基因芯片 实时荧光定量聚合酶链反应 

分 类 号：R338.26[医药卫生—人体生理学]