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氧化苦参碱抑制异丙肾上腺素诱导大鼠慢性心力衰竭及对ADMA代谢通路的影响
引用本文:王洋,徐烨华,熊爱琴,袁娅妮,郑萍,马萍,戴贵东,徐清斌.氧化苦参碱抑制异丙肾上腺素诱导大鼠慢性心力衰竭及对ADMA代谢通路的影响[J].中国中药杂志,2014,39(3):471-477.
作者姓名:王洋  徐烨华  熊爱琴  袁娅妮  郑萍  马萍  戴贵东  徐清斌
作者单位:宁夏医科大学 药学院 药理学系, 宁夏 银川 750004;宁夏医科大学 总医院 心内科, 宁夏 银川 750004;宁夏医科大学 总医院 心内科, 宁夏 银川 750004;宁夏医科大学 药学院 药理学系, 宁夏 银川 750004;宁夏医科大学 药学院 药理学系, 宁夏 银川 750004;宁夏医科大学 总医院 心内科, 宁夏 银川 750004;凯里学院 化学与材料工程学院 制药工程系, 贵州 凯里 556011;宁夏医科大学 总医院 心内科, 宁夏 银川 750004
基金项目:国家自然科学基金项目(81060024)
摘    要:目的:探讨氧化苦参碱抑制异丙肾上腺素(ISO)诱导大鼠慢性心力衰竭及其对非对称二甲基精氨酸(ADMA)代谢通路的影响。 方法:雄性Sprague-Dawley大鼠,皮下注射ISO 5 mg·kg-1·d-1,连续给药7 d诱发大鼠慢性心力衰竭。氧化苦参碱(100,50 mg·kg-1)于ISO注射前7 d灌胃给药,共14 d。检测血清学指标、心功能血流动力学参数、心脏质量,并观察心肌组织病理变化,同时采用Western blotting法测定相关蛋白的表达。 结果:氧化苦参碱(100,50 mg·kg-1)可显著降低ISO诱导的心力衰竭大鼠升高的血清心肌肌钙蛋白I(cTn I)水平,改善左心室收缩和舒张功能及左心室重构,显著减轻ISO致大鼠心肌的病理学改变。还可降低ISO诱导心力衰竭大鼠血清ADMA含量(P<0.01),增加心室肌组织中二甲基二甲胺水解酶2(DDAH2)蛋白的表达(P<0.01),但对ISO诱导升高的蛋白精氨酸甲基转移酶1(PRMT1)无影响。 结论:氧化苦参碱可改善ISO诱导的慢性心力衰竭大鼠的心功能,抑制心室重构,其作用机制与降低血清ADMA水平和增高心肌组织DDAH2表达水平有关。

关 键 词:氧化苦参碱  异丙肾上腺素  慢性心力衰竭  ADMA  PRMT1  DDAH2
收稿时间:2013/11/6 0:00:00

Protective effect of oxymatrine on chronic heart failure and ADMA metabolism pathway in isoproterenol-induced chronic heart failure in rats
WANG Yang,XU Ye-hu,XIONG Ai-qin,YUAN Ya-ni,ZHENG Ping,MA Ping,DAI Gui-dong and XU Qing-bin.Protective effect of oxymatrine on chronic heart failure and ADMA metabolism pathway in isoproterenol-induced chronic heart failure in rats[J].China Journal of Chinese Materia Medica,2014,39(3):471-477.
Authors:WANG Yang  XU Ye-hu  XIONG Ai-qin  YUAN Ya-ni  ZHENG Ping  MA Ping  DAI Gui-dong and XU Qing-bin
Institution:Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China;Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China;Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China;Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China;Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China;Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China;Department of Pharmaceutical Engineering, School of Chemical and Materials Engineering, Kaili University, Kaili 556011, China;Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China
Abstract:Objective: To investigate the protective effects of oxymatrine on chronic heart failure induced by isoproterenol (ISO) and to observe its effects on ADMA metabolism pathway in ISO-induced chronic heart failure in rats. Method: Male Sprague-Dawley rats were given oxymatrine (100,50 mg·kg-1) orally for 14 days. Heart failure was induced in rats by subcutaneous injection of isoproterenol (5 mg·kg-1·d-1) at the 8th day for 1 week. Serum parameters, haemodynamic parameters, Heart weight, and histopathological variables were analysed. Expression of protein levels were measured by Western blot. Result: Oxymatrine (100,50 mg·kg-1) significantly attenuated serum content of cTn I, improved left ventricle systolic and diastolic function and left ventricular remodeling, reduced the ISO-induced myocardial pathological changes compared with ISO group. In addition, oxymatrine (100,50 mg·kg-1) significantly reduced serum level of ADMA (P<0.01), normalize the reduced dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression (P<0.01), but had no effect on the isoproterenol-induced upregulated protein arginine methyltransferases 1 expression. Conclusion: Oxymatrine could ameliorate the experimental ventricular remodeling in ISO-induced chronic heart failure in rats and the mechanism involved in reducing serum content of ADMA and increased DDAH2 expression.
Keywords:oxymatrine  isoproterenol  chronic heart failure  ADMA  PRMT1  DDAH2
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