注射用益气复脉(冻干)不同给药途径对心力衰竭大鼠的药效作用对比研究  

Comparative study on pharmacological effects of Yiqi Fumai Lyophilized Injection through different administration routes on heart failure rats

作　　者：魏栋 李智 万梅绪[3,4] 张燕欣 庄朋伟 李德坤[3,4] 鞠爱春[3,4] WEI Dong;LI Zhi;WAN Meixu;ZHANG Yanxin;ZHUANG Pengwei;LI Dekun;JU Aichun(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Inner Mongolia Medical University,Hohhot 010107,China;Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of Traditional Chinese Medicine Injections,Tianjin 300410,China)

机构地区：[1]天津中医药大学,天津301617 [2]内蒙古医科大学,内蒙古呼和浩特010107 [3]天津天士力之骄药业有限公司,天津300410 [4]天津市中药注射剂安全性评价企业重点实验室,天津300410

出　　处：《药物评价研究》2023年第8期1665-1672,共8页Drug Evaluation Research

摘　　要：目的探讨注射用益气复脉(冻干)(YQFM)不同给药途径对心力衰竭大鼠的药效。方法将70只经腹主动脉结扎造成心力衰竭模型的SD大鼠随机分为7组: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),益气复脉胶囊组(ig益气复脉胶囊246.3 mg·kg^(-1)+尾iv 0.9%氯化钠注射液),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),联合给药组(ig卡托普利片3.35 mg·kg^(-1)+尾iv YQFM 464.3 mg·kg^(-1)),另取10只进行切口不进行结扎SD大鼠为假手术组(ig+尾iv 0.9%氯化钠注射液)。分别于给药后1 h的第1、3、5、7、14天眼内眦取血,酶联免疫吸附试验(ELISA)法检测大鼠血清中心钠肽(ANP)、脑钠肽(BNP)、内皮素(ET)水平;连续给药14 d,给药结束后对各组大鼠进行心脏超声检测;取出心脏,HE染色后观察病理变化。结果与模型组相比,给药后1 d,YQFM尾iv低、高剂量组及卡托普利片组和联合给药组血清ANP水平显著降低(P<0.05、0.01),YQFM尾iv低、高剂量组和联合给药组血清BNP、ET水平显著降低(P<0.05);给药后7、14 d,各给药组血清ANP、BNP、ET水平显著降低(P<0.05、0.001);各给药组的左室短轴缩短率(LVFS)、左室射血分数(LVEF)、E峰与A峰的比值(E/A)均显著上升(P<0.001);各给药组心肌细胞病理变化有明显好转。与YQFM ig组相比,给药后1 d YQFM尾iv低、高剂量组和给药后14 d YQFM尾iv低剂量组血清ANP水平显著降低(P<0.05);给药后1、7 d YQFM尾iv低、高剂量组和给药后14 d YQFM尾iv低剂量组血清BNP水平显著降低(P<0.05、0.01、0.001);给药1 d YQFM尾iv低、高剂量组和给药7、14 d YQFM尾iv低剂量组血清ET水平显著降低(P<0.05、0.001);YQFM尾iv低、高剂量组的E/A均显著升高(P<0.05、0.001)。结论不同给药途径的YQFM均可以对Objective To investigate the comparative study on the pharmacodynamic effects of Yiqi Fumai Lyophilized Injection(YQFM)on rats with heart failure by different administration routes.Method Seventy SD rats with heart failure model induced by abdominal aorta ligation were randomly divided into seven groups: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 clinical equivalent dose),Yiqi Fumai Capsule group(ig Yiqi Fumai Capsule 246.3 mg·kg^(-1)+tail iv 0.9%sodium chloride injection),YQFM ig group(ig YQFM 464.3 mg·kg^(-1)+tail iv 0.9%sodium chloride injection),captopril tablet group(ig captopril tablet 3.35 mg·kg^(-1)+tail iv 0.9%sodium chloride injection),combined administration group(ig captopril tablet 3.35 mg·kg^(-1)+tail iv YQFM 464.3 mg·kg^(-1)),and 10 other SD rats without ligation of the incision were taken as sham-operated group(ig+tail iv 0.9%sodium chloride injection).On the 1st,3rd,5th,7th,and 14th day after administration,blood was collected from the inner canthus of the eyes,and the serum levels of central natriuretic peptide(ANP),brain natriuretic peptide(BNP),and endothelin(ET)were measured using enzyme-linked immunosorbent assay(ELISA).Continuous administration for 14 days,followed by cardiac ultrasound testing of rats in each group after administration.Take out the heart and observe the pathological changes after HE staining.Result Compared with model group,one day after administration,the serum ANP levels in the YQFM tail iv low-dose and high-dose groups,the captopril tablet group and the combined administration group were significantly lower(P<0.05,0.01),and the serum BNP and ET levels in the YQFM tail iv low-dose and high-dose groups and the combined administration group were significantly lower(P<0.05).At 7 and 14 days after administration,the levels of serum ANP,BNP,and ET in each treatment group were significantly reduced(P<0.05,0.001).Compared with model group,the le

关 键 词：不同给药途径 注射用益气复脉(冻干) 心力衰竭 心功能 尾静脉注射 灌胃 

分 类 号：R285.5[医药卫生—中药学]