基于线粒体凋亡通路探讨抗纤益心方对转基因扩张型心肌病小鼠的影响

Study on the Effect of Kangxian Yixin Formula on Transgenic Dilated Cardiomyopathy Mice Based on Mitochondrial Apoptosis Pathway

目的:探讨抗纤益心方对转基因扩张型心肌病小鼠(DCM)的影响及作用机制。方法:将30只cTnT^(R141W)转基因小鼠随机分为模型组、抗纤益心方(20.4 g/kg)组及辅酶Q10(1.5 mg/kg)组,每组10只,选择同期C57BL/6J小鼠10只作为正常对照组。适应性喂养1 w后开始灌胃,正常对照组和模型组灌胃相应体积生理盐水。连续干预8 w后检测小鼠心脏超声相关指标,HE和Masson染色观察心肌组织病理学变化,电镜检查心肌细胞线粒体超微结构,Western Blot检测心肌组织Cyp-D、Cyt-C、Caspase-3蛋白表达。结果:与正常对照组比较,模型组小鼠心功能显著降低(P<0.01),心肌病理损害严重,线粒体结构紊乱,Cyp-D、Cyt-C、Caspase-3蛋白表达显著升高(P<0.05)。与模型组比较,抗纤益心方组和辅酶Q10组心功能显著好转(P<0.05或P<0.01),心肌组织病理损伤明显减轻,心肌细胞线粒体结构较完整,Cyp-D、Cyt-C、Caspase-3蛋白表达显著降低(P<0.05)。结论:抗纤益心方能通过调节线粒体凋亡通路改善DCM小鼠心肌损害,从而发挥治疗作用。

Objective:To explore the effect of Kangxian yixin formula on transgenic dilated cardiomyopathy(DCM)mice and its mechanism.Methods:Thirty cTnT^(R141W)transgenic mice were randomly divided into model group,Kangxian yixin formula(20.4 g/kg)group and Coenzyme Q10(1.5 mg/kg)group,each with 10 mice,10 same period C57 BL/6 J mice were selected as the normal control group.After one week of adaptive feeding,the normal control group and model group were intfagastric with the corresponding volume of normal saline.After 8 weeks of continuous intervention,related indexes of cardiac ultrasound in mice were detected.HE and Masson staining were used to observe the pathological changes of myocardial tissue.Mitochondrial ultrastructure of myocardial cells was examined by electron microscopy.Protein expressions of Cyp-D,Cyt-C and Caspase-3 in myocardial tissue were detected by Western Blot.Results:Compared with the normal control group,the cardiac function of mice in model group was signficantiy decreased(P<0.01),the myocardial pathological damage was serious,the mitochondrial structure was disorder,and the protein expressions of Cyp-D,Cyt-C and Caspase-3 were signficantiy increased(P<0.05).Compared with model group,the cardiac function of mice in Kangxian yixin formula and Coenzyme Q10 groups was significantly improved(P<0.05 or P<0.01),the pathological damage of myocardial tissue was significantly reduced,the mitochondrial structure of myocardial cells was intact,and the protein expressions of Cyp-D,Cyt-C and Caspase-3 were signficantiy decreased(P<0.05).Conclusion:Kangxian yixin formula can improve myocardial damage in DCM mice by regulating the mitochondrial apoptosis pathway,thereby exerting a therapeutic effect.