目的 比较注射用益气复脉（冻干，YQFM）尾iv和ig给药途径对sc异丙肾上腺素（ISO）诱导心肌梗死大鼠的药效作用，探讨YQFM注射途径在治疗心肌梗死上的必要性。方法 通过sc ISO制备心肌梗死大鼠模型，将造模成功的70只大鼠随机分为：模型组（ig＋尾iv 0.9%氯化钠注射液），YQFM尾iv低、高剂量组（ig 0.9%氯化钠注射液＋尾iv YQFM 464.3、928.6 mg·kg⁻¹，低剂量为临床等效剂量），YQFM ig组（ig YQFM 464.3 mg·kg⁻¹＋尾iv 0.9%氯化钠注射液），盐酸曲美他嗪组（ig盐酸曲美他嗪5.35 mg·kg⁻¹＋尾iv 0.9%氯化钠注射液）；10只假手术（sc 0.9%氯化钠注射液）组大鼠ig＋尾iv 0.9%氯化钠注射液，连续给药14 d。分别在给药第1、3、5、7、14天进行超声心动检测；利用ELISA试剂盒检测大鼠给药第1、3、5、7、14天血清天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肌钙蛋白T（cTnT）、肿瘤坏死因子-α（TNF-α）水平。末次给药结束后，检测大鼠心电图；取出心脏，利用苏木精-伊红（HE）染色考察YQFM对心脏组织病理形态学的影响。结果 超声心动检测结果显示，尾iv途径与模型组相比在第5天或者第7天见效（P＜0.05、0.01、0.001），比口服途径起效更快、效果更好（P＜0.05、0.01、0.001）。心电图检测结果显示，与假手术组相比，造模后心电图紊乱，ST波下降，给予各组药物后，与模型组相比，注射途径ST波明显升高，尾iv组比YQFM ig组更明显。生化指标检测结果显示，在AST、ALT、CK-MB、LDH、SOD、MDA、cTnT、TNF-α指标中，尾iv途径与ig途径相比起效更快、疗效更好（P＜0.05、0.01、0.001）。HE结果显示，假手术组心肌细胞排列整齐，模型组有心肌细胞溶解和出血现象，给予各组药物后溶解和出血现象减轻，改善心肌细胞。结论 不同给药途径的YQFM均可以对心肌梗死大鼠发挥治疗作用，尾iv途径比ig途径治疗效果更好，也能更早发挥药效。

Objective To investigate the efficacy of different administration routes of Yiqi Fumai Lyophilized Injection (YQFM) in rats with model of myocardial infarction was induced by subcutaneous injection of isoproterenol, and whether YQFM is necessary in the treatment of myocardial infarction by injection route. Methods A myocardial infarction rat model was prepared using sc isoproterenol, and 70 successfully modeled rats were randomly divided into: model group (ig+tail iv 0.9% sodium chloride injection), YQFM tail iv low and high dose groups (ig 0.9% sodium chloride injection+tail iv YQFM 464.3, 928.6 mg·kg⁻¹, low dose is the clinical equivalent dose), YQFM ig group (ig YQFM 464.3 mg·kg⁻¹+tail iv 0.9% sodium chloride injection), and trimetazidine hydrochloride group (ig trimetazidine hydrochloride 5.35 mg·kg⁻¹+tail iv 0.9% sodium chloride injection); 10 rats in the sham surgery group received ig+tail iv 0.9% sodium chloride injection, continuous administration for 14 days. Echocardiography was performed on days 1,3,5,7, and 14 after the first administration. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), CK-MB, LDH, superoxide dismutase (SOD), MDA, cardiac troponin T (cTnT) and tumor necrosis factor-α (TNF-α) in serum of rats on 1, 3, 5, 7 and 14 days were detected by ELISA kit. After the last administration, the electrocardiogram of the rats was detected, and the heart was taken out. HE staining was used to investigate the effect of YQFM on the pathomorphology of heart tissue. Preliminary evaluation of the pharmacodynamic effects of YQFM with different administration routes on myocardial ischemia rats. Results In the experiment of myocardial infarction rat model induced by subcutaneous injection of isoproterenol, the results of echocardiography showed that the injection route was effective on the 5th or 7th day compared with the model group (P < 0.05, 0.01, 0.001), and the effect was faster than the oral route, and there was a significant difference compared with the oral route (P < 0.05, 0.01, 0.001). The results of electrocardiogram showed that compared with the sham operation group, the electrocardiogram was disordered and the ST wave decreased after modeling. After administration of each group of drugs, the injection route was significantly higher than that of the model group (P < 0.001). Compared with the YQFM ig group, there were significant differences (P < 0.01, 0.001). The results of biochemical indicators showed that among AST, ALT, CK-MB, LDH, SOD, MDA, cTnT and TNF-α, the injection route had faster onset and better efficacy than the oral route (P < 0.05, 0.01, 0.001). HE results showed that the myocardial cells in the sham operation group were arranged neatly, and the myocardial cells in the model group were dissolved and bleeding. After administration of drugs in each group, the dissolution and bleeding were reduced and the myocardial cells were improved. Conclusion Different administration routes of YQFM can play a therapeutic role in rats with myocardial infarction. The tail iv route is better than the ig route, and it can also play a therapeutic role earlier.

R285.5

天津市制造业高质量发展专项资金—天津天士力之骄药业有限公司技术中心创新能力建设（ZZY20232088）