心梗后心室重构中Hsp20的作用及补阳还五汤的调控

Ventricular remodeling after myocardial infarction has the key role of heart failure. BuYang Huanwu decoction(BYHWD) made a good effect of treatment ventricular remodeling after myocardial infarction in clinic. According to the results of BYHWD prefeasibility study, we hypothesis that the treatment effects of BYHWD in ventricular remodeling may regulation of heat shock protein 20 (Hsp20); Hsp20 may be the potential preventional targets ventricular remodeling after myocardial infarction . This project is the RNA interference, echocardiogram, histopathological staining, Western-Blot and Real Time-PCR technology, such as for BYHWD decoction of targeted silence of the Hsp20 ventricular remodeling after myocardial infarction rat models of heart structure and function, myocardial cell apoptosis and collagen reconstruction role. Clear up BYHWD is the regulation mechanism, to explore the treatment of ventricular remodeling after myocardial infarction targets and effective drugs, rich Chinese medicine treatment mechanism.

心室重构是心梗后发生心衰的关键环节，对其防治具有重要的意义。补阳还五汤从益气活血立法处方治疗心梗后心室重构在临床上取得良好疗效。依据前期对补阳还五汤抗心室重构疗效以及机制的研究结果，推测：补阳还五汤抗心室重构作用可能和上调热休克蛋白20(Hsp20)的表达有关；Hsp20可能是防治心梗后心室重构的潜在靶点。本项目拟采用RNA干扰、心脏超声、组织病理学染色、Western-Blot及Real Time-PCR等技术，观察补阳还五汤对靶向沉默的Hsp20在心梗后心室重构模型大鼠心脏结构及功能、心肌细胞凋亡及胶原重构的作用。明确补阳还五汤对Hsp20的调控机制，进一步发掘心梗后心室重构的治疗靶点及有效药物，丰富中药治疗的疗效机理。

背景：心室重构是心衰、猝死，是远期发生心源性死亡的最重要的危险因素。补阳还五汤是治疗心梗后心室重构的有效药物，但其机制尚不明确。.主要研究内容：课题组通过大鼠心梗及氧化应激诱导的H9C2心肌细胞损伤模型，采用慢病毒载体、Western Blot、RT-PCR等技术，对Hsp20在心梗后心室重构中的作用及激活Hsp20在补阳还五汤抗心肌细胞凋亡中的作用进行探索。.结果：1. 补阳还五汤能降低心脏重量/体重比,降低左室舒张末内径、左收缩末内径，增加了左心室射血分数、短轴缩短率。2.补阳还五汤能抑制心梗后心肌细胞凋亡，增加Bcl-2的表达，抑制Bax表达及Caspase3的活性。3.补阳还五汤升高心梗后左室心肌Hsp20的表达。4.补阳还五汤能剂量依赖性的抑制H2O2诱导心肌细胞凋亡，并上调Hsp20的表达5.成功构建RNA干扰Hsp20的H9C2心肌细胞系，LV.Hsp20-321组比对照组的Hsp20表达下降90%。6.抑制Hsp20部分阻断了补阳还五汤的心脏保护作用。.结论：激活Hsp20在补阳还五汤的心肌保护中发挥重要的作用。补阳还五汤的抗心梗后心事重构作用可能与激活Hsp20有关。