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

Zhen Ci Yan Jiu. 2021 Nov 25;46(11):935-41. doi: 10.13702/j.1000-0607.201219.
[Article in Chinese]

Abstract

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=10 rats per group). The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride solution (DOX, 2.5 mg/kg) twice a week for 4 weeks. After successful modeling, the rats in the normal and model groups were fed with normal diet, and fixed on a rat plate for 20 min each time without any treatment. Mild moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min each time, for 3 weeks in the moxibustion and moxibustion+benazepril groups. Rats of the benazepril and moxibustion+benazepril groups received gavage of benazepril (2 mg/kg) once daily for 3 weeks. 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-18 expression 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 NT-proBNP content, and myocardial IL-18 expression 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-18 expression 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-18 expression and increasing p-Akt expression in myocardial tissue.

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”,20 min/次;贝那普利组予贝那普利(2 mg/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。.

Keywords: Cardiac function; Chronic heart failure; Interleukin-18; Moxibustion; Protein kinase B.

MeSH terms

  • Animals
  • Benzazepines
  • Heart Failure* / genetics
  • Heart Failure* / therapy
  • Interleukin-18
  • Male
  • Moxibustion*
  • Proto-Oncogene Proteins c-akt / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Benzazepines
  • Interleukin-18
  • Proto-Oncogene Proteins c-akt
  • benazepril