[關(guān)鍵詞]
[摘要]
目的 探討注射用益氣復(fù)脈(凍干)(YQFM)不同給藥途徑對(duì)心力衰竭大鼠的藥效。方法 將70只經(jīng)腹主動(dòng)脈結(jié)扎造成心力衰竭模型的SD大鼠隨機(jī)分為7組: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),益氣復(fù)脈膠囊組(ig益氣復(fù)脈膠囊246.3 mg·kg-1+尾iv 0.9%氯化鈉注射液),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),聯(lián)合給藥組(ig卡托普利片3.35 mg·kg-1+尾iv YQFM 464.3 mg·kg-1),另取10只進(jìn)行切口不進(jìn)行結(jié)扎SD大鼠為假手術(shù)組(ig+尾iv 0.9%氯化鈉注射液)。分別于給藥后1 h的第1、3、5、7、14天眼內(nèi)眥取血,酶聯(lián)免疫吸附試驗(yàn)(ELISA)法檢測(cè)大鼠血清中心鈉肽(ANP)、腦鈉肽(BNP)、內(nèi)皮素(ET)水平;連續(xù)給藥14 d,給藥結(jié)束后對(duì)各組大鼠進(jìn)行心臟超聲檢測(cè);取出心臟,HE染色后觀察病理變化。結(jié)果 與模型組相比,給藥后1 d,YQFM尾iv低、高劑量組及卡托普利片組和聯(lián)合給藥組血清ANP水平顯著降低(P<0.05、0.01),YQFM尾iv低、高劑量組和聯(lián)合給藥組血清BNP、ET水平顯著降低(P< 0.05);給藥后7、14 d,各給藥組血清ANP、BNP、ET水平顯著降低(P<0.05、0.001);各給藥組的左室短軸縮短率(LVFS)、左室射血分?jǐn)?shù)(LVEF)、E峰與A峰的比值(E/A)均顯著上升(P<0.001);各給藥組心肌細(xì)胞病理變化有明顯好轉(zhuǎn)。與YQFM ig組相比,給藥后1 d YQFM尾iv低、高劑量組和給藥后14 dYQFM尾iv低劑量組血清ANP水平顯著降低(P<0.05);給藥后1、7 d YQFM尾iv低、高劑量組和給藥后14 d YQFM尾iv低劑量組血清BNP水平顯著降低(P<0.05、0.01、0.001);給藥1 d YQFM尾iv低、高劑量組和給藥7、14 d YQFM尾iv低劑量組血清ET水平顯著降低(P<0.05、0.001); YQFM尾iv低、高劑量組的E/A均顯著升高(P<0.05、0.001)。結(jié)論 不同給藥途徑的YQFM均可以對(duì)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。
[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.
[中圖分類(lèi)號(hào)]
R285.5
[基金項(xiàng)目]