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强心汤对慢性心力衰竭大鼠线粒体的影响及机制
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| 篇名： | 强心汤对慢性心力衰竭大鼠线粒体的影响及机制 |
| TITLE： | Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure |
| 摘要： | 目的 探讨强心汤对慢性心力衰竭（CHF）大鼠线粒体的影响及潜在机制。方法采用结扎冠状动脉左前降支的方法建立CHF模型。将造模成功的大鼠分为模型组，强心汤低、高剂量组（12.25、24.50g/kg，以生药量计），化学药组（沙库巴曲缬沙坦钠片，10.42mg/kg），另设不作处理的对照组，每组10只。各组大鼠灌胃相应药液或生理盐水，每天2次，连续28d。末次给药后，检测大鼠血清中氨基末端脑利钠肽前体（NT-proBNP）、三磷酸腺苷（ATP）和心肌组织中磷脂酸（PA）、心磷脂（CL）含量；观察大鼠心肌组织病理损伤和胶原纤维化情况；检测大鼠心肌细胞凋亡情况；观察心肌组织超微结构；检测心肌组织中线粒体融合蛋白1（Mfn1）、Mfn2、视神经萎缩蛋白1（OPA1）、动力相关蛋白1（Drp1）的表达情况。结果与对照组比较，模型组大鼠血清中NT-proBNP含量，心肌细胞凋亡率，心肌组织中S-OPA1、Drp1蛋白的相对表达量均显著升高（P＜0.05）；血清中ATP含量，心肌组织中PA、CL含量和Mfn1、Mfn2、L-OPA1蛋白的相对表达量均显著降低（P＜0.05）；心肌组织各层膜组织结构异常，心肌细胞变性坏死，且纤维化严重；心肌组织线粒体可见肿胀，嵴减少或消失，基质密度不均匀。经强心汤干预后，大鼠血清及心肌组织中上述定量指标水平（强心汤低剂量组CL含量除外）均显著逆转（P＜0.05）；心肌组织病理损伤明显改善，纤维化情况明显减轻；线粒体形态趋于正常且嵴增多，基质密度均匀。结论强心汤可调节CHF大鼠的心肌线粒体功能和结构完整性，进而改善心肌能量代谢，减轻心肌纤维化；其作用机制可能与激活PA/Mfn/CL信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway. |
| 期刊： | 2025年第36卷第02期 |
| 作者： | 毛美玲；卢健棋；朱智德；庞延；谢丽钰；陈佳永；吴鑫宇；肖湘；卢俊燊；石炜琦 |
| AUTHORS： | MAO Meiling， LU Jianqi，ZHU Zhide，PANG Yan，XIE Liyu，CHEN Jiayong，WU Xinyu，XIAO Xiang，LU Junshen，SHI Weiqi |
| 关键字： | 强心汤；慢性心力衰竭；线粒体；能量代谢；纤维化；PA/Mfn/CL信号通路 |
| KEYWORDS： | Qiangxin decoction； chronic heart failure； mitochondrion； energy metabolism； fibrosis； PA/Mfn/CL signaling |
| 阅读数： | 4 次 |
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