大鼠急性肾缺血再灌注损伤早期的基因表达  

Genes Expression in the Early Stage of Acute Renal Ischemia-reperfusion Injury in Rats

作　　者：林俊毅[1] 茅幸[2] 吴慧娟[2] 薛爱民[1] 

机构地区：[1]复旦大学基础医学院法医学系,上海200032 [2]复旦大学基础医学院病理学系,上海200032

出　　处：《法医学杂志》2016年第6期401-405,409,共6页Journal of Forensic Medicine

基　　金：上海市科委科创项目(15140902900)

摘　　要：目的研究急性肾缺血再灌注损伤早期的差异基因表达,探索其潜在的分子机制。方法通过单纯夹闭大鼠肾动脉制备肾缺血再灌注模型,进行基因表达芯片检测和生物信息学分析,筛选急性肾损伤早期的差异基因表达及其所涉及的细胞活动和信号通路。同时,通过构建差异表达基因的生物网络来寻找与急性肾损伤关系密切的分子,并进行荧光定量PCR验证。结果在检测出的151个差异表达基因中,132个基因显著上调,19个基因显著下调,GO与KEGG通路富集分析结果显示主要与细胞增殖、细胞因子介导的信号通路和免疫反应等有关。荧光定量PCR结果显示,与对照组相比,挑选出的3个与急性肾损伤高度相关的基因(ANXA1、PHLDA1、KLF6)在疾病早期具有显著的表达差异,上升倍数与芯片检测出的倍数基本一致。结论本研究揭示了急性肾损伤早期的差异基因表达特征以及所涉及的生物学过程和信号通路,其中ANXA1、PHLDA1、KLF6可能在急性肾损伤的发病机制中起到一定作用。Objective To study the differential genes expression in the early stage of acute renal ischemiareperfusion injury and explore potential molecular mechanisms. Methods The ischemia-reperfusion model was made via clamping renal artery of rat. The microarray detection and bioinformatics analyzing of the genes expression were performed. Differentially expressed genes were screened and related cellular activi-ties and signaling pathways were analyzed in early stage of acute kidney injury. Meanwhile, molecules closely relative to acute kidney injury were explored by establishing a biological network of the differen-tially expressed genes, and the results were verified by real-time PCR. Results A total of 151 genes showed differential expression in this study, including 132 up-regulated and 19 down-regulated genes. Cell proliferation, cytokines mediated signaling transduction and immune responses were greatly enriched by GO and KEGG analysis. The results of real-time PCR showed that compared with control groups, three selected genes （ANXA1, PHLDA1 and KLF6） which related to the acute kidney injury had an ob-vious differential expression in the early stage of disease. The multiple of increase was essentially the same as the multiple detected by microarray. Conclusion This study shows differential gene expression profile, related biological processes and signaling pathways involved in the early stage of acute kidney injury. ANXA1, PHLDA1 and KLF6 may play a role in the pathogenesis of acute kidney injury.

关 键 词：法医病理学 再灌注损伤 差异基因表达 生物信息学 

分 类 号：R692.9[医药卫生—泌尿科学]