Yuan Ya-Hui, Yuan Rong, Miao Yu, Wang Ya, Li Peng-Qi, Hui Jia-Qi, Pan Yu-Fan, Li Zi-Han, Xin Qi-Qi, Cong Wei-Hong
Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China National Clinical Research Center for Chinese Medicine Cardiology Beijing 100091, China.
Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.
Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(19):5292-5298. doi: 10.19540/j.cnki.cjcmm.20220325.702.
This study aims to investigate the effects and the underlying mechanism of Huangqi Shengmai Decoction(HQSMD) in the treatment of fatigue and myocardial injury in a joint rat model. Wistar rats were assigned into 4 groups: sham, model, diltiazem hydrochloride(positive control), and HQSMD. The joint model of fatigue and myocardial injury was established by 14-day exhausted swimming followed by high ligation of the left anterior descending coronary artery. The rats in the sham group underwent a sham operation without coronary artery ligation or swimming. Since the fourth day after the ligation, swimming was continued in the model group and the drug-treated groups for the following 4 weeks. Meanwhile, the rats in the positive control group and the HQSMD group were respectively administrated intragastrically with diltiazem hydrochloride(20 mg·kg(-1)·d(-1)) and HQSMD(0.95 g·kg(-1)·d(-1)) for 4 weeks, while the shams and the models were given the same volume of normal saline. The left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), grip strength, and myocardial pathophysiological changes were measured to evaluate the anti-fatigue and cardioprotective effects of HQSMD. The protein levels of PTEN-induced putative kinase 1(PINK1) and parkin in the myocardium were measured by Western blot to preliminarily elucidate the mechanism of HQSMD in ameliorating myocardial injury by suppressing mitochondrial autophagy. Compared with the shams, the models showed weakened heart function(LVEF and LVFS, P<0.01), decreased grasping ability(P<0.05), elevated blood urea nitrogen(BUN) and aldosterone(ALD) levels(P<0.01), aggravated myocardial fibrosis and connective tissue hyperplasia(P<0.01), and up-regulated protein levels of PINK1(P<0.01) and parkin(P<0.05). Four-week treatment with HQSMD increased the LVEF and LVFS levels(P<0.01), enhanced the grip strength(P<0.01), reduced the serum levels of BUN(P<0.01) and ALD(P<0.05), alleviated the pathological injury and fibrosis in the myocardium(P<0.01), and down-regulated the protein levels of PINK1(P<0.01) and parkin(P<0.05) in heart tissue. The results demonstrate that HQSMD may alleviate myocardial fibrosis and protect myocardium by suppressing the excessive mitochondrial auto-phagic activity and reducing the excessively elevated ALD level, thereby ameliorating fatigue and myocardial injury.
本研究旨在探讨黄芪生脉饮（HQSMD）对联合大鼠疲劳及心肌损伤模型的治疗作用及其潜在机制。将Wistar大鼠分为4组：假手术组、模型组、盐酸地尔硫䓬（阳性对照组）和HQSMD组。通过14天的疲劳游泳，随后高位结扎左冠状动脉前降支，建立疲劳和心肌损伤联合模型。假手术组大鼠仅接受假手术，不进行冠状动脉结扎或游泳。自结扎后第4天起，模型组和药物治疗组大鼠继续游泳4周。同时，阳性对照组和HQSMD组大鼠分别灌胃给予盐酸地尔硫䓬（20 mg·kg⁻¹·d⁻¹）和HQSMD（0.95 g·kg⁻¹·d⁻¹），持续4周，而假手术组和模型组大鼠给予等量生理盐水。测量左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）、握力及心肌病理生理变化，以评估HQSMD的抗疲劳和心脏保护作用。采用蛋白质免疫印迹法检测心肌中PTEN诱导激酶1（PINK1）和帕金森蛋白的水平，初步阐明HQSMD通过抑制线粒体自噬改善心肌损伤的机制。与假手术组相比，模型组大鼠心功能减弱（LVEF和LVFS，P<0.01），抓握能力下降（P<0.05），血尿素氮（BUN）和醛固酮（ALD）水平升高（P<0.01），心肌纤维化和结缔组织增生加重（P<0.01），PINK1蛋白水平上调（P<0.01），帕金森蛋白水平上调（P<0.05）。HQSMD治疗4周后，LVEF和LVFS水平升高（P<0.01），握力增强（P<0.01），血清BUN水平降低（P<0.01），ALD水平降低（P<0.05），心肌病理损伤和纤维化减轻（P<0.01），心脏组织中PINK1蛋白水平下调（P<0.01），帕金森蛋白水平下调（P<0.05）。结果表明，HQSMD可能通过抑制过度的线粒体自噬活性和降低过高的ALD水平，减轻心肌纤维化，保护心肌，从而改善疲劳和心肌损伤。
