[关键词]
[摘要]
目的 对比注射用益气复脉(冻干,YQFM)尾iv和ig给药途径对左前降支结扎心力衰竭大鼠的药效,探讨YQFM注射途径在治疗心力衰竭上的必要性。方法 构建冠状动脉左前降支结扎心力衰竭大鼠模型,将造模成功的70只大鼠分为: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),卡托普利片组(ig卡托普利片3.35 mg·kg−1+尾iv 0.9%氯化钠注射液);10只假手术组进行切口不结扎(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左室射血分数(LVEF)、短轴收缩率分数(LVFS)、二尖瓣E峰/二尖瓣A峰(E/A);利用试剂盒检测大鼠给药第1、3、5、7、14天的血清心钠素(ANP)、脑钠尿肽(BNP)、肌钙蛋白(Tn)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、抗环胍氨酸肽(CCP)水平;末次给药结束后,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,在LVEF、LVFS、E/A指标中,尾iv途径与模型组相比在第3天或者第5天见效(P<0.05、0.01、0.001),比ig途径起效更快,与ig途径相比改善作用更明显,显著性差异(P<0.05、0.01、0.001)。生化指标检测结果显示,在ANP、BNP、Tn、LDH、CK-MB、CCP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,假手术组大鼠心肌细胞排列整齐,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均可以对心力衰竭大鼠发挥治疗作用,尾iv途径比ig途径治疗效果更好,也能更早发挥药效。
[Key word]
[Abstract]
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.
[中图分类号]
R285.5
[基金项目]
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)