心力衰竭大鼠心肌SERCA2a和miR-25-3p/5p表达的改变及泻肺利水方药的干预作用

Expressions of SERCA2a and miR-25-3p/5p in myocardium of rats with heart failure and therapeutic effects of Xiefei Lishui recipe

目的:观察心力衰竭大鼠肌浆网钙ATP酶(SERCA2a)mRNA和mi R-25-3p/5p表达水平的变化及中药泻肺利水方药的干预作用。方法:SD大鼠随机分为对照组、模型组、中药组、卡托普利组和地高辛组(n=10),阿霉素腹腔注射(总剂量15 ml/kg,2周内分6次注射)建立心力衰竭大鼠模型,5周后分别以蒸馏水(10 ml/(kg·d))、泻肺利水中药(22 g/(kg·d))、卡托普利(19 mg/(kg·d))和地高辛(32μg/(kg·d))连续灌胃35 d,观察大鼠心肌SERCA2a mRNA、mi R-25-3p/5p的表达水平和SERCA2a活性、血浆脑钠肽水平、心输出量和射血分数。结果:模型组大鼠心输出量和射血分数显著降低,心肌SERCA2a mRNA表达水平和活性降低,mi R-25-3p和mi R-25-5p的表达水平、血浆脑钠肽水平显著升高;泻肺利水中药能提高心肌SERCA2a mRNA表达水平和活性,降低mi R-25-3p和mi R-25-5p的表达水平,降低血浆脑钠肽水平,提高心输出量和射血分数;卡托普利能提高心肌SERCA2a mRNA表达水平,降低mi R-25-3p和mi R-25-5p的表达水平,降低血浆脑钠肽水平,提高心输出量;地高辛能提高心肌SERCA2a mRNA表达水平,降低血清脑钠肽水平,提高心输出量。结论:心力衰竭大鼠心肌SERCA2a mRNA的表达下调,mi R-25-3p和mi R-25-5p的表达上调;泻肺利水方药可以上调SERCA2a mRNA的表达,下调心肌mi R-25-3p和mi R-25-5p的表达,改善心功能。

Objective： To investigate the expressions of sarcoplasmic reticulum calcium ATPase 2a （SERCA2a） mRNA and miR-25-3p/ 5p in myocardium of rats with heart failure and the therapeutic effects of Xiefei Lishui recipe（Traditional Chinese Medicine）. Methods： SD rats were randomly divided into five groups： control group, model group, Traditional Chinese Medicine group（TCM group）, captopril group and digoxin group（ n = 10）. Heart failure rat model was induced by intraperitoneal injections of doxorubicin（6 injections within 2 weeks; total dose： 15 mg/kg）. Five weeks after the first injection, Distilled water（ 10 ml/（kg· d） ）, TCM（22 g/（kg· d） ）, eaptopril（ 19 mg/（kg· d） ）, and digoxin（32 ktg,/（ kg· d））were administrated by gastrogavagc for 35 days, respectively. Myocardial expressions of SERCA2a mRNA and miR-25- 3p/5p were detected; myocardial activities of SERCA2a were measured; cardiac output（CO） and left ventricular ejection fraction（LVEF） and plasma level of B-type natriuretic peptide （BNP） were measured. Results： Myocardial mRNA expression of SERCA2a was significantly down- regulated in rats with heart failure which could be significantly up-regulated by TCM or captopril or digoxin, while expressions of miR-25-3p and miR-25-5p in myocardium were significantly up-regulated which could be significantly down-regulated by TCM or captopril. SERCA2a activity, CO and LVEF in rats with heart failure were decreased significantly which could be significantly increased by TCM, while plasma level of BNP was increased significantly which could be significantly decreased by TCM or captopril or digoxin. CO in rats with heart failure could be significantly increased by captopril or digoxin. Condusion： In rats with heart failure, myocardial mRNA expression of SERCA2a was downregulated, expression of miR-25-3p and miR-25-5p in myocardium was upregulated. Xiefei Lishui recipecan upregulate myocardial mRNA expression of SERCA2a, downregulate expression of miR-25-3p and miR-25-5p in myocardium and improve cardiac function.