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

doi:10.12047/j.cjap.5449.2017.037

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (2): 146-150.doi: 10.12047/j.cjap.5449.2017.037

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

吴锦波^1,2, 叶小汉², 冼绍祥³, 董明国²

1. 广州中医药大学博士后流动站, 广州 510405;
2. 东莞市中医院心内科, 东莞 523000;
3. 广州中医药大学第一附属医院心内科, 广州 510405

收稿日期:2016-04-19 修回日期:2016-11-21 出版日期:2017-03-28 发布日期:2018-06-20
通讯作者: 冼绍祥,Tel:020-36598909,E-mail:shaoxiangx@hotmail.com E-mail:shaoxiangx@hotmail.com
基金资助:
冼绍祥,Tel:020-36598909,E-mail:shaoxiangx@hotmail.com

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

WU Jin-bo^1,2, YE Xiao-han², XIAN Shao-xiang³, DONG Ming-guo²

1. Post-doctoral Research Station of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405;
2. Department of Cardiology, Dongguan Hospital of Traditional Chinese Medicine, Dongguan 523000;
3. Department of Cardiology, the First Clinical Medical Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, China

Received:2016-04-19 Revised:2016-11-21 Online:2017-03-28 Published:2018-06-20
Contact: 冼绍祥,Tel:020-36598909,E-mail:shaoxiangx@hotmail.com E-mail:shaoxiangx@hotmail.com
Supported by:
冼绍祥,Tel:020-36598909,E-mail:shaoxiangx@hotmail.com

摘要/Abstract

摘要： 目的：观察心力衰竭大鼠肌浆网钙ATP酶（SERCA2a） mRNA和miR-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SERCA2amRNA、miR-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，miR-25-3p和miR-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miR-25-3p和miR-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miR-25-3p和miR-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，miR-25-3p和miR-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miR-25-3p和miR-25-5p的表达，改善心功能。

关键词: 泻肺利水方药, 心力衰竭, 肌浆网钙ATP酶, miRNA-25, 大鼠

Abstract: 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)), captopril(19 mg/(kg·d)),and digoxin(32μg/(kg·d))were administrated by gastrogavage 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 signifi-cantly increased by captopril or digoxin. Conclusion: 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.

Key words: Xiefei Lishui recipe, heart failure,congestive, sarcoplasmic reticulum calcium ATPase, miRNA-25, mouse

吴锦波, 叶小汉, 冼绍祥, 董明国. 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[J]. 中国应用生理学杂志, 2017, 33(2): 146-150.

WU Jin-bo, YE Xiao-han, XIAN Shao-xiang, DONG Ming-guo. Expressions of SERCA2a and miR-25-3p/5p in myocardium of rats with heart failure and therapeutic effects of Xiefei Lishui recipe[J]. CJAP, 2017, 33(2): 146-150.

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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

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