目的 探究注射用益气复脉（冻干）在改善心梗后所致慢性心力衰竭（chronic heart failure，CHF）大鼠的作用及机制。方法 将冠状动脉左前降支手术结扎造模成功后的75只SD大鼠随机分为模型组，益气复脉低、高剂量（464.3、928.6 mg/kg）组，卡托普利（3.35 mg/kg）组和益气复脉（464.3 mg/kg）+卡托普利（3.35 mg/kg）组，另取15只仅切口缝合但不结扎的SD大鼠作为假手术组。给予药物干预2周后，用小动物超声诊断仪检测大鼠心功能；采用ELISA试剂盒检测各组大鼠血清中心钠肽（atrial natriuretic peptide，ANP）、脑钠肽（brain natriuretic peptide，BNP）、内皮素-1（endothelin-1，ET-1）、心肌肌钙蛋白（cardiac troponin，cTn）、白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、三磷酸腺苷（adenosine triphosphate，ATP）含量和肌酸激酶（creatine kinase，CK）、肌酸激酶同工酶（creatine kinase isoenzyme-MB，CK-MB）、超氧化物歧化酶（superoxide dismutase，SOD）活力；采用苏木素-伊红（HE）染色法观察各组大鼠心脏组织病理变化；采用Western blotting检测各组大鼠心脏中能量代谢相关蛋白表达。结果 与假手术组比较，模型组大鼠心功能指标左室射血分数（LVEF）、二尖瓣血流频谱E峰/A峰（E/A）和左室短轴缩短率（LVFS）均明显下降（P＜0.001），血清中ANP、BNP、cTn、ET-1、IL-6、TNF-α水平和CK、CK-MB活力均显著升高（P＜0.001），SOD活性和ATP水平显著下降（P＜0.001），左心室组织出现心肌纤维断裂及心肌细胞变性、坏死等病理改变，心脏中磷酸腺苷激活的蛋白激酶（AMP-activated protein kinase，AMPK）、p-AMPK、葡萄糖转运蛋白-4（glucose transporter-4，GLUT-4）和肉碱棕榈酰转移酶-1（carnitine palmitoyltransferase-1，CPT-1）蛋白表达水平均显著降低（P＜0.05、0.01、0.001）。与模型组比较，各给药组LVEF、E/A和LVFS均显著提高（P＜0.05、0.01、0.001），血清中ANP、BNP、cTn、ET-1、IL-6、TNF-α水平和CK-MB、CK活力均显著降低（P＜0.05、0.01、0.001），ATP水平和SOD活力显著升高（P＜0.01、0.001），大鼠心肌损伤得到明显改善，心脏中p-AMPK、AMPK、GLUT-4和CPT-1蛋白表达水平均显著升高（P＜0.05、0.01、0.001）。结论 益气复脉可以通过提高CHF大鼠的射血分数和舒缩功能改善心功能，通过降低大鼠血清心肌损伤、氧化应激水平并改善能量代谢，从而改善CHF大鼠心衰症状，改善能量代谢可能是其重要的作用机制之一。

Objective To explore the pharmacodynamic effect and mechanism of Yiqi Fumai Lyophilized Injection (注射用益气复脉, YQFM) on improving rats with chronic heart failure (CHF) caused by myocardial infarction. Methods Seventy-five SD rats were randomly divided into model group, YQFM low-and high-dose (464.3, 928.6 mg/kg) groups, captopril (3.35 mg/kg) and YQFM (464.3 mg/kg) + captopril (3.35 mg/kg) group, and 15 SD rats with incision suture but no ligation were selected as sham group. After two weeks of drug intervention, the cardiac function of rats was detected by small animal ultrasonic diagnostic instrument. Levels of central natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1), cardiac troponin (cTn), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), adenosine triphosphate (ATP) and creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), superoxide dismutase (SOD) activities in serum were detected by ELISA; HE staining was used to observe the pathological changes of heart tissue in rats in each group. Western blotting was used to detect the expressions of energy metabolism-related proteins in hearts of rats in each group. Results Compared with sham group, the left ventricular ejection fraction (LVEF), E/A peak of mitral flow spectrum (E/A) and shortening rate of left ventricular short axis (LVFS) in model group were significantly decreased (P < 0.001), levels of ANP, BNP, cTn, ET-1, IL-6, TNF-α and CK activity in serum were significantly increased (P < 0.001), SOD activity and ATP level were significantly decreased (P < 0.001), pathological changes such as myocardial fiber breakage, myocardial cell degeneration and necrosis occurred in the left ventricle, AMP-activated protein kinase (AMPK), p-AMPK, glucose transporter-4 (GLUT-4) and carnitine palmitoyl transferase-1 (CPT-1) protein expression levels were significantly decreased (P < 0.05, 0.01, 0.001). Compared with model group, LVEF, E/A and LVFS in each administration group were significantly increased (P < 0.05, 0.01, 0.001), levels of ANP, BNP, cTn, ET-1, IL-6, TNF-α and CK-MB and CK activities in serum were significantly decreased (P < 0.05, 0.01, 0.001), SOD activity and ATP level were significantly increased (P < 0.01, 0.001), myocardial injury in rats was obviously improved, p-AMPK, AMPK, GLUT-4 and CPT-1 protein expression levels in heart were significantly increased (P < 0.05, 0.01, 0.001). Conclusion YQFM can improve cardiac function by increasing ejection fraction and systolic and diastolic function in CHF rats, and improve heart failure symptoms and energy metabolism by reducing serum myocardial injury and oxidative stress levels in CHF rats, which may be one of its important mechanisms.

R285.5

国家重点研发计划项目（2019YFC1710005）；国家自然科学基金资助项目（82205081）；中国博士后科学基金第16批特别资助项目（2023T160069）；2021年度科技协同创新专项（XTCX2021-09）