目的 對比注射用益氣復(fù)脈（凍干，YQFM）尾iv和ig給藥途徑對左前降支結(jié)扎心力衰竭大鼠的藥效，探討YQFM注射途徑在治療心力衰竭上的必要性。方法 構(gòu)建冠狀動脈左前降支結(jié)扎心力衰竭大鼠模型，將造模成功的70只大鼠分為：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），卡托普利片組（ig卡托普利片3.35 mg·kg⁻¹＋尾iv 0.9%氯化鈉注射液）；10只假手術(shù)組進(jìn)行切口不結(jié)扎（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)行超聲心動檢測左室射血分?jǐn)?shù)（LVEF）、短軸收縮率分?jǐn)?shù)（LVFS）、二尖瓣E峰/二尖瓣A峰（E/A）；利用試劑盒檢測大鼠給藥第1、3、5、7、14天的血清心鈉素（ANP）、腦鈉尿肽（BNP）、肌鈣蛋白（Tn）、乳酸脫氫酶（LDH）、肌酸激酶同工酶（CK-MB）、抗環(huán)胍氨酸肽（CCP）水平；末次給藥結(jié)束后，取出心臟，利用蘇木精-伊紅（HE）染色考察YQFM對心臟組織病理形態(tài)學(xué)的影響。結(jié)果 超聲心動檢測結(jié)果顯示，在LVEF、LVFS、E/A指標(biāo)中，尾iv途徑與模型組相比在第3天或者第5天見效（P＜0.05、0.01、0.001），比ig途徑起效更快，與ig途徑相比改善作用更明顯，顯著性差異（P＜0.05、0.01、0.001）。生化指標(biāo)檢測結(jié)果顯示，在ANP、BNP、Tn、LDH、CK-MB、CCP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)組大鼠心肌細(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均可以對心力衰竭大鼠發(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 left anterior descending ligation heart failure, and whether YQFM is necessary in the treatment of heart failure by injection route.Methods A rat model of left anterior descending coronary artery ligation induced heart failure was constructed, and 70 successfully modeled rats were 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 Captopril Tablet group (ig Captopril Tablets 3.35 mg·kg⁻¹ + tail iv 0.9% sodium chloride injection), continuous administration for 14 days. Ten sham surgery groups underwent incision without ligation (ig + tail iv 0.9% sodium chloride injection). Echocardiography was performed on days 1, 3, 5, 7, and 14 after the first administration to measure left ventricular ejection fraction (LVEF), short axis systolic fraction (LVFS), and mitral valve E/A peak (E/A). The levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), troponin (Tn), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB) and anti-cyclic guanosine peptide (CCP) in serum of rats on 1, 3, 5, 7 and 14 days were detected by kits. After the last administration, the heart was taken out, and the effect of YQFM on the pathomorphology of heart tissue was investigated by hematoxylin-eosin (HE) staining. Results In the experiment of rat model of heart failure caused by left anterior descending coronary artery ligation, the results of echocardiography showed that the injection route was effective on the 3rd or 5th day compared with the model group (P < 0.05, 0.01, 0.001), 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 biochemical indicators showed that in ANP, BNP, Tn, LDH, CK-MB and CCP indicators, the injection route had a 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 routes of administration of YQFM can play a therapeutic role in rats with heart failure. The tail iv route is better than the ig route, and it can also play a therapeutic effect earlier.

R285.5

天津市制造業(yè)高質(zhì)量發(fā)展專項資金—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）