[关键词]
[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 dYQFM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 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 left ventricular short axis shortening rate (LVFS), left ventricular ejection fraction (LVEF), and the ratio of E peak to A peak (E/A) in all groups increased significantly (P<0.001). Compared with model group, the pathological changes of myocardial cells in each treatment group were significantly improved. Compared with the YQFM ig group, the serum ANP levels in the low-dose and high-dose YQFM tail iv groups one day after administration and the low-dose YQFM tail iv group 14 days after administration were significantly reduced (P<0.05), the serum BNP levels in the low-dose and high-dose YQFM tail iv groups at 1 and 7 days after administration, as well as the low-dose YQFM tail iv group at 14 days after administration were significantly reduced (P<0.05, 0.01, 0.001), the serum ET levels were significantly reduced in the low-dose and high-dose YQFM tail iv groups after one day of administration, as well as in the low-dose YQFM tail iv groups after 7 and 14 days of administration (P<0.05, 0.001). Compared with the YQFM ig group, The E/A levels in both low-dose and high-dose YQFM tail iv groups were significantly increased (P<0.05, 0.001). Conclusion YQFM of different route of administration can play a therapeutic role in heart failure rats, and the tail iv route was better than the ig route, and can also play a role earlier.
[中图分类号]
R285.5
[基金项目]