强心汤对慢性心力衰竭大鼠心肌线粒体稳态和能量代谢的影响  

Effects of Qiangxin decoction on myocardial mitochondrial homeostasis and energy metabolism in chronic heart failure rats

作　　者：庞延 毛美玲 卢健棋[3] 陈佳永 唐梅玲 黄溥玮 PANG Yan;MAO Meiling;LU Jianqi;CHEN Jiayong;TANG Meiling;HUANG Puwei(Dept.of Emergency,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530001,China;Graduate School,Guangxi University of Chinese Medicine,Nanning 530001,China;Cardiovascular Zone 1,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530001,China)

机构地区：[1]广西中医药大学第一附属医院急诊科,南宁530001 [2]广西中医药大学研究生院,南宁530001 [3]广西中医药大学第一附属医院心血管一区,南宁530001

出　　处：《中国药房》2024年第15期1831-1836,共6页China Pharmacy

基　　金：广西自然科学基金项目(No.2021GXNSFBA196018,No.2021GXNSFAA220111);国家自然科学基金项目(No.82160887);国家中医药传承创新中心项目(No.2023019-10);广西岐黄学者培养项目(No.2024005-06-02)。

摘　　要：目的基于线粒体自噬,探讨强心汤对慢性心力衰竭(CHF)大鼠心肌线粒体稳态和能量代谢的影响。方法取雄性SD大鼠,通过结扎左冠状动脉前降支构建CHF模型,并将造模成功的大鼠按随机数字表法分为模型组、强心汤组[12.25 g/(kg·d),按生药量计]、卡托普利组[10.38 mg/(kg·d)]、强心汤+卡托普利组(用法用量同各单药组),每组8只;另取正常大鼠8只,仅于左冠状动脉前降支穿线但不结扎,作为假手术组。从造模成功次日开始,各药物组大鼠每天分2次灌胃相应药液,连续28 d。末次给药后,检测梗死心肌组织中腺苷三磷酸(ATP)、腺苷一磷酸(AMP)、游离脂肪酸(FFA)水平,观察其病理改变和线粒体形态,检测其B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、TANK结合激酶1(TBK1)、p62蛋白的表达情况。结果与假手术组比较,模型组大鼠心肌组织纤维化明显,大量线粒体肿胀、融合,内嵴断裂;梗死心肌组织中AMP、FFA水平和Bax、p62蛋白的表达均显著升高或上调,ATP水平和Bcl-2、TBK1蛋白的表达均显著降低或下调(P<0.05)。与模型组比较,各药物组大鼠心肌组织病理改变和线粒体肿胀均有所改善,梗死心肌组织中AMP、FFA水平和Bax、p62蛋白的表达均显著降低或下调(P<0.05),ATP水平和Bcl-2、TBK1蛋白的表达均显著升高或上调(P<0.05),且强心汤+卡托普利组的效果优于各单药组(P<0.05)。结论强心汤能够减轻CHF大鼠心肌纤维化、线粒体肿胀,改善其心肌能量代谢;上述作用可能与调控Bcl-2、Bax、TBK1、p62蛋白表达,促进心肌线粒体自噬有关。OBJECTIVE To investigate the effects of Qiangxin decoction on myocardial mitochondrial and energy metabolism in rats with chronic heart failure(CHF)based on mitophagy.METHODS Male SD rats were collected to establish CHF model by ligating the left anterior descending branch of coronary artery.The successful modeling rats were divided into model group,Qiangxin decoction group[12.25 g/(kg·d),calculated by crude drug],captopril group[10.38 mg/(kg·d)],and Qiangxin decoction+captopril group(the same usage and dosage as single drug group)according to a random number table method,with 8 rats in each group.Another 8 normal rats were selected and received threading in the left anterior descending branch of the coronary artery without ligation as the sham operation group.Starting from the second day after successful modeling,the rats in administration groups were given relevant drug intragastrically,twice a day,for consecutive 28 days.After the last medication,the levels of adenosine triphosphate(ATP),adenosine monophosphate(AMP)and free fatty acid(FFA)in infarcted myocardial tissues were detected,the pathological changes and mitochondrial morphology of the infarcted myocardial tissue were observed,as well as the protein expressions of B cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax),TANK-binding kinase 1(TBK1),p62 were detected in each group.RESULTS Compared with the sham operation group,the infarcted myocardial tissue fibrosis was changed evidently,with a large number of mitochondrial swelling and fusion,and internal cristae rupture;the levels of AMP and FFA,the protein expressions of Bax and p62 were all increased or up-regulated significantly in infarcted myocardial tissue,while the level of ATP,and the protein expressions of Bcl-2 and TBK1 were all decreased or down-regulated significantly(P<0.05).Compared with the model group,the pathological changes of infarcted myocardial tissue and mitochondrial swelling had been improved;the levels of AMP and FFA,and the protein expressions of Bax and p62 in infarcted myoca

关 键 词：强心汤 慢性心力衰竭 线粒体自噬 线粒体稳态 能量代谢 

分 类 号：R285[医药卫生—中药学] R256.2[医药卫生—中医学]