TRAIL及其受体DR5在病毒性心肌炎小鼠心肌组织中的表达和意义

Expression and significance of TRAIL and its receptor DR5 in murine myocardium with acute viral myocarditis

目的 研究肿瘤坏死因子相关的凋亡诱导配体（TRAIL）及其死亡受体5（DR5）在病毒性心肌炎小鼠心肌组织中病变不同时期的表达及与细胞凋亡的关系.方法 建立病毒性心肌炎小鼠模型,于注射病毒后第7、10、14、21、28天取心肌组织,HE染色做心肌病理积分,TUNEL法检测凋亡细胞百分率,免疫组织化学法和逆转录-聚合酶链反应（RT-PCR）检测心肌组织中TRAIL和DR5蛋白及mRNA的表达.结果 病毒感染组小鼠和正常对照组小鼠心肌组织中均存在TRAIL和DR5蛋白和mRNA的表达.病毒感染后第14天,病毒感染组小鼠心肌组织中TRAIL蛋白表达高于同期正常对照组（P〈0.05）和第7天病毒感染组（P〈0.05）,组间比较差异有统计学意义（F=9.17,P〈0.01）.病毒感染后第10、14、21天,病毒感染组小鼠DR5蛋白表达高于同期正常对照组（P〈0.01）和第7天病毒感染组（P〈0.01）,组间比较差异有统计学意义（F=13.32,P〈0.01）.且TRAIL和DR5蛋白的表达与心肌病理积分、心肌细胞凋亡率密切相关（P〈0.05）.病毒感染组第10天TRAIL mRNA表达高于同期正常对照组（P〈0.01）和第7天病毒感染组（P〈0.01）,组间比较差异有统计学意义（F=10.86,P〈0.01）.病毒感染组第10、14天DR5 mRNA表达高于同期正常对照组（P〈0.01）和第7天病毒感染组（P〈0.01）,组间比较差异有统计学意义（F=22.75,P〈0.01）.结论 病毒性心肌炎小鼠发病中期,TRAIL及其受体DR5在心肌组织中出现高表达,且与病理积分、心肌细胞凋亡率成正相关,TRAIL及其受体DR5可能通过调控心肌细胞凋亡参与病毒性心肌炎的病理过程.

Objective To deterine the expression of TNF-related apoptosis inducing ligand （TRAIL） and its receptor DR5 in murine myocardium with acute viral myocarditis（VM）.Methods We builted the model of VM.Eight mice of the VM group and the normal control group were sacrificed on the 7th,10th,14th,21st,28th day after inoculation CVB3 virus.The myocardial histopathological scores were counted.The terminal reansferase-mediated dUPT-biotin nick end-labeling （TUNEL） assays was used to quantified apoptosis rate.The expression of TRAIL and DR5 protein and mRNA were determined by the method of immunohistochemistry and reverse-transcription polymerase chain reaction （RT-PCR）.Results The expression of TRAIL and DR5 protein and mRNA were found in myocardium of both the normal control group and the VM group.The expression of TRAIL protein of the VM group（14th） were significantly higher than which in the normal group at the same time and the VM group（7th）（F=9.17,P〈0.01）.The DR5 protein of the VM group（10th,14th,21st）were significantly higher than which in the normal group at the same time and the VM group（7th）（F=13.32,P〈0.01）.The expression of TRAIL and DR5 protein were positive correlated with the myocardial histopathological scores and the apoptosis rate.The expression of TRAIL mRNA of the VM group（10th） were significantly higher than which in the normal group at the same time and the VM group（7th）（F=10.86,P〈0.01）.The DR5 mRNA of the VM group（10th,14th）were significantly higher than which in the normal group at the same time and the VM group（7th）（F=22.75,P〈0.01）.Conclusion High characteristic expressions of protein/mRNA TRAIL and DR5 were observed in the myocardium of mice with VM.The level was positive correlationed with the account of pathology and the rate of apoptosis.The apoptosis induced by TRAIL and DR5 may participate in the pathophysiological processes of VM.