艾灸联合贝那普利对慢性心力衰竭大鼠心肌组织白细胞介素-18及磷酸化蛋白激酶B表达水平的影响

Effect of moxibustion combined with benazepril on expression of IL-18and phosphorylated protein kinase B in myocardial tissue of rats with chronic heart failure

目的:观察艾灸联合贝那普利对慢性心力衰竭(CHF)大鼠心功能及心肌组织白细胞介素-18(IL-18)、磷酸化蛋白激酶B(p-Akt)表达水平的影响,探讨艾灸联合贝那普利防治CHF的可能机制。方法:SD大鼠随机分为正常组10只和造模组40只。造模组大鼠采用腹腔隔日注射盐酸多柔比星制备CHF模型。造模成功的存活大鼠随机分为模型组、艾灸组、贝那普利组、艾灸+贝那普利组(艾贝组),每组各9只。艾灸组予艾条温和灸双侧“肺俞”“心俞”,20min/次;贝那普利组予贝那普利(2mg/kg)灌胃;艾贝组先予贝那普利灌胃,再行艾灸;均每日1次,连续3周。观察大鼠的一般情况;超声心动图检查大鼠射血分数(EF)、左室内径缩短率(FS)、左室舒张末径(LVIDd)、左室收缩末径(LVIDs)、心率(HR)、室间隔厚度(IVS);酶联免疫吸附法检测血清N末端脑钠素前体(NT-proBNP)含量;蛋白免疫印迹法检测心肌组织IL-18、p-Akt表达水平。结果:与正常组比较,模型组大鼠EF、FS、IVS和心肌组织p-Akt表达水平显著降低(P<0.01),LVIDd、LVIDs、HR、血清NT-proBNP含量、心肌组织IL-18表达水平显著升高(P<0.01)。与模型组比较,艾灸组、贝那普利组、艾贝组EF、FS、IVS和心肌组织p-Akt表达水平升高(P<0.05,P<0.01),LVIDd、LVIDs、HR、血清NT-proBNP含量、心肌组织IL-18表达水平降低(P<0.05,P<0.01)。与艾贝组比较,艾灸组、贝那普利组EF、FS、IVS、心肌组织p-Akt表达水平显著降低(P<0.01),LVIDs、HR、血清NT-proBNP含量、心肌组织IL-18表达水平升高(P<0.05,P<0.01)。结论:艾灸联合贝那普利改善CHF大鼠心功能,其机制可能是通过降低心肌组织中IL-18表达和升高p-Akt,且表达优于单用艾灸和贝那普利。

Objective To observe the effect of moxibustion combined with benazepril on cardiac function and expression levels of myocardial interleukin-18(IL-18),phosphorylated protein kinase B(p-Akt)in rats with chronic heart failure(CHF),so as to explore its underlying mechanisms in improvement of CHF.Methods Fifty male rats were randomly divided into normal,model,moxibustion,benazepril and moxibustion+benazepril groups(n=10rats per group).The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride solution(DOX,2.5mg/kg)twice a week for 4weeks.After successful modeling,the rats in the normal and model groups were fed with normal diet,and fixed on a rat plate for 20min each time without any treatment.Mild moxibustion was applied to bilateral“Feishu”(BL13)and“Xinshu”(BL15)for 20min each time,for 3weeks in the moxibustion and moxibustion+benazepril groups.Rats of the benazepril and moxibustion+benazepril groups received gavage of benazepril(2mg/kg)once daily for 3weeks.The general behaviors of rats were observed.The ejection fraction(EF),left ventricular diameter shortening(FS),left ventricular end-diastolic diameter(LVIDd),left ventricular end-systolic diameter(LVIDs),heart rate(HR)and ventricular septal thickness(IVS)were examined by echocardiography.The content of serum N-terminal pro brain natriuretic peptide(NT-proBNP)was detected by enzyme-linked immunosorbent assay,and expression levels of myocardial IL-18,p-Akt were detected by Western blot.Results Compared with the normal group,the EF,FS,IVS,and myocardial p-Akt expression level were significantly reduced(P<0.01),and the LVIDd,LVIDs,HR,and serum NT-proBNP content and myocardial IL-18expression level were significantly increased in the model group(P<0.01).In comparison with the model group,the EF,FS,IVS,and myocardial p-Akt were remarkably up-regulated(P<0.05,P<0.01),and the LVIDd,LVIDs,HR,serum NTproBNP content,and myocardial IL-18expression level were significantly down-regulated(P<0.05,P<0.01)in the moxibustion,benazepril,and moxibustion+benazepril groups.Compared with the moxibustion+benazepr group,the levels of LVIDs,HR,serum NT-proBNP and myocardial IL-18expression were obviously higher(P<0.05,P<0.01),while the levels of EF,FS,IVS and p-Akt were significantly lower in the moxibustion and benazepril groups(P<0.01).Conclusion Moxibustion combined with benazepril improves cardiac function in CHF rats,and is superior to simple moxibustion and simple benazepril in reducing IL-18expression and increasing p-Akt expression in myocardial tissue.