目的 比較注射用益氣復(fù)脈（凍干，YQFM）尾iv和ig給藥途徑對(duì)sc異丙腎上腺素（ISO）誘導(dǎo)心肌梗死大鼠的藥效作用，探討YQFM注射途徑在治療心肌梗死上的必要性。方法 通過sc ISO制備心肌梗死大鼠模型，將造模成功的70只大鼠隨機(jī)分為：模型組（ig＋尾iv 0.9%氯化鈉注射液），YQFM尾iv低、高劑量組（ig 0.9%氯化鈉注射液＋尾iv YQFM 464.3、928.6 mg·kg⁻¹，低劑量為臨床等效劑量），YQFM ig組（ig YQFM 464.3 mg·kg⁻¹＋尾iv 0.9%氯化鈉注射液），鹽酸曲美他嗪組（ig鹽酸曲美他嗪5.35 mg·kg⁻¹＋尾iv 0.9%氯化鈉注射液）；10只假手術(shù)（sc 0.9%氯化鈉注射液）組大鼠ig＋尾iv 0.9%氯化鈉注射液，連續(xù)給藥14 d。分別在給藥第1、3、5、7、14天進(jìn)行超聲心動(dòng)檢測(cè)；利用ELISA試劑盒檢測(cè)大鼠給藥第1、3、5、7、14天血清天冬氨酸氨基轉(zhuǎn)移酶（AST）、丙氨酸氨基轉(zhuǎn)移酶（ALT）、肌酸激酶同工酶（CK-MB）、乳酸脫氫酶（LDH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肌鈣蛋白T（cTnT）、腫瘤壞死因子-α（TNF-α）水平。末次給藥結(jié)束后，檢測(cè)大鼠心電圖；取出心臟，利用蘇木精-伊紅（HE）染色考察YQFM對(duì)心臟組織病理形態(tài)學(xué)的影響。結(jié)果 超聲心動(dòng)檢測(cè)結(jié)果顯示，尾iv途徑與模型組相比在第5天或者第7天見效（P＜0.05、0.01、0.001），比口服途徑起效更快、效果更好（P＜0.05、0.01、0.001）。心電圖檢測(cè)結(jié)果顯示，與假手術(shù)組相比，造模后心電圖紊亂，ST波下降，給予各組藥物后，與模型組相比，注射途徑ST波明顯升高，尾iv組比YQFM ig組更明顯。生化指標(biāo)檢測(cè)結(jié)果顯示，在AST、ALT、CK-MB、LDH、SOD、MDA、cTnT、TNF-α指標(biāo)中，尾iv途徑與ig途徑相比起效更快、療效更好（P＜0.05、0.01、0.001）。HE結(jié)果顯示，假手術(shù)組心肌細(xì)胞排列整齊，模型組有心肌細(xì)胞溶解和出血現(xiàn)象，給予各組藥物后溶解和出血現(xiàn)象減輕，改善心肌細(xì)胞。結(jié)論 不同給藥途徑的YQFM均可以對(duì)心肌梗死大鼠發(fā)揮治療作用，尾iv途徑比ig途徑治療效果更好，也能更早發(fā)揮藥效。

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

天津市制造業(yè)高質(zhì)量發(fā)展專項(xiàng)資金—天津天士力之驕藥業(yè)有限公司技術(shù)中心創(chuàng)新能力建設(shè)（ZZY20232088）