自发性糖尿病大鼠心肌物质代谢及细胞增殖相关基因的表达谱研究  

Alteration of substance metabolism and cell proliferation related gene expression in myocardial tissue of diabetic rats

作　　者：王东[1] 张伟伟[1] 周丽诺[1] 钟慈声[2] 胡仁明[1] 

机构地区：[1]复旦大学附属华山医院内分泌科,200040 [2]复旦大学上海医学院电镜室,上海200032

出　　处：《复旦学报（医学版）》2007年第2期187-192,共6页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(30270627)

摘　　要：目的研究自发性糖尿病(OLETF)大鼠发生心肌病变后基因表达谱的改变。方法①检测糖尿病大鼠与对照组大鼠的心室压,并比较两者的电镜标本;②从心肌组织中抽提纯化总RNA,逆转录合成两组动物的cDNA及cRNA探针,与基因表达谱芯片杂交,扫描并分析统计。结果①糖尿病大鼠的-dp/dtmax,左室内压峰值明显小于对照组,EDP明显高于对照组;电镜提示糖尿病大鼠存在心肌肌纤维扭曲断裂,线粒体变性,间质增生及血管基底膜增厚;②糖尿病大鼠心肌中调控细胞增殖分化基因上调表达;胰岛素信号通路PI3K调节亚基基因及部分参与糖、脂代谢基因的表达明显下调。结论糖尿病大鼠存在心肌超微结构改变和心肌舒张功能下降,表达谱中PI3K调节亚基及物质代谢、细胞增殖相关基因表达异常。Purpose To study the alteration of gene expression spectrum in myocardium of diabetic rats when the ultramicrostructure disorder and dysfunction were found. Methods The rats were sacrificed after detecting left ventricular pressure. Myocardial tissues at the apex were obtained for electronmicroscope study. The probes were made by rat cRNAs of RT-PCR and transcription products. The target arrays were hybridized to a eukaryotic GeneChip probe array and then the signals were scanned and analyzed. Results Electronmicroscopy revealed a spectrum of subcellular remodeling in myocardium, which was characterized by damaged myofibrils and mitochondria. The -dp/dt max and the peak pressure were lower and the EDP was higher in diabetic rats than that in control rats. The cell proliferation related genes were up-regulation expression. Down-regulation expression genes were PI3K subunit and some substance metabolism related genes in diabetic rats. Conclusions The myocardia in diabetic rats exhibited myocardial ultramicrostructure, ventricular function abnormal with substance metabolism and cell proliferation related genes disorders.

关 键 词：糖尿病 心肌/心肌病 细胞增殖 物质代谢 基因表达 

分 类 号：R587.1[医药卫生—内分泌]