肠道病毒感染心肌组织基因异常表达及与心肌疾病关系

Enteroviruses are the most common cause of virus myocarditis.The persistent enterovires infection contributes to the pathogensis of human DCM, However,the mechanisms by which vireses cause myocarditis or DCM are not well understood. The cDNA microarrys , real-time RT-PCR and bioinformative analysis techniques have be used though the project for orderliness of genes expression profiling in BALB/C mice with CVB3 infcetion(acute phase,chronic phase and dilated cardiomyopathy) The results showed that 736 genes were abnormity,which 185,upregulated,551.downregulated, in myocardium tissues gene expression in 3 days post-infection with CVB3 compared to control;568 genes , abnormity, which215, upregulated, 353, downregulated, in 7 days post-infection; 358 genes, abnormity,which 166, upregulated, 200, downregulated, in 21 days post-infection , respectively. Altered expression of genes included stress, immune response, metabolized, inflammation, apoptosis, signal transduction pathways and cytoskeleton proteins.There were certainly relations between the affected genes and viral persistence and histopathology. Bag-1, known to be involved in inhibition of apoptosis , was investigated further. The results showed that Bag-1 expression was down-regulated by up to 30% in virus-infected mouse heart on day 7,Down regulated expression and distribution of Bag-1 protein or evidence of apoptosis in the infected mouse was demonstrated. This project studied changes in the expression and adjust of cardiac genes and influence on the heart functions resulting from CVB3 infected of mice. This may be important for exploring the pathogenesis of viral myocarditis, dilated cadiomyopathy with heart failure,discovering potential antiviral targets and new drug development.

用cDNA-Array技术和蛋白质双向凝胶电泳等方法在离体培养大鼠心肌细胞和小鼠模型中分析和确定因肠道病毒感染而异常表达的主要心肌组织基因及其调节因素，研究这些基因异常表达与病毒性心肌疾病（心肌炎和心肌病）关系，并在病毒性心肌疾病患者心肌中进一步验证。本研究对病毒性心肌病发病机理阐明、疾病相关基因研究和治疗药物开发等有重要意义。.