当归补血汤通过调控Ca^(2+)-SERCA2a抑制肥厚型心肌病大鼠内质网应激反应改善心肌损伤

Danggui Buxue Decoction(当归补血汤)Inhibits Endoplasmic Reticulum Stress in HCM Rats by Regulating Ca^(2+)-SERCA2a and Improves Myocardial Injury

目的观察当归补血汤对肥厚型心肌病(HCM)大鼠心室重构及心功能的改善作用,初步探讨Ca^(2+)-SERCA2a在其中的调控机制,为临床中药复方防治HCM提供理论依据。方法 SPF级SD大鼠30只,随机分为假手术组(Sham组),肥厚性心肌病模型组(HCM组),肥厚性心肌病模型+当归补血汤干预组(DGBXT组),采用主动脉缩窄法建立HCM大鼠模型,超声心动图评价大鼠心脏结构及心功能变化,HE、Masson染色观察大鼠心肌组织病理学改变,ELISA检测氧化应激因子表达,免疫荧光观察心肌组织中ROS表达,Western Blot检测心肌组织中内质网应激相关蛋白GRP78、Caspase-12、SERCA2a表达。结果当归补血汤可以抑制大鼠心室重构,提高LVEF、LVFS水平,缓解心肌细胞损伤及心肌纤维,同时上调SOD、Cat、GRP78、SERCA2a表达,下调MDA、ROS、Caspase-12表达。结论当归补血汤可以显著改善HCM大鼠心室重构及心功能损伤,其作用机制可能与其调控Ca^(2+)-SERCA2a抑制HCM大鼠内质网应激反应有关。

Objective To observe the effect of Danggui Buxue Decoction(当归补血汤) on ventricular remodeling and cardiac function in hypertrophic cardiomyopathy(HCM) rats and preliminary explore the regulatory mechanism of Ca^(2+)-SERCA2 a in it, so as to provide a theoretical basis for the prevention and treatment of HCM with traditional Chinese medicine. Methods Thirty SPF SD rats were randomly divided into sham operation group(Sham group), hypertrophic cardiomyopathy model group(HCM group), hypertrophic cardiomyopathy model+Danggui Buxue Decoction intervention group(DGBXD group). Arterial constriction method was used to establish HCM rat model. Echocardiography was used to evaluate the changes of heart structure and cardiac function. HE and Masson staining were used to observe the pathological changes of myocardial tissue. ELISA was used to detect the expression of oxidative stress factor. Immunofluorescence was used to observe the ROS expression in myocardial tissue. Western blot detected expressions of endoplasmic reticulum stress-related proteins GRP78, Caspase-12 and SERCA2 a in myocardial tissue. Results Danggui Buxue Decoction can inhibit ventricular remodeling in rats, increase the levels of LVEF and LVFS, alleviate myocardial cell damage and myocardial fibers, and at the same time up-regulate expressions of SOD, Cat, GRP78 and SERCA2 a, and down-regulate expressions of MDA, ROS and Caspase-12. Conclusion Danggui Buxue Decoction can significantly improve ventricular remodeling and cardiac function injury in HCM rats, and its mechanism may be related to its regulation of Ca^(2+)-SERCA2 a inhibiting endoplasmic reticulum stress response in HCM rats.