王洋;徐烨华;熊爱琴;袁娅妮;郑萍;马萍;戴贵东;徐清斌;
WANG Yang;XU Ye-hua;XIONG Ai-qin;YUAN Ya-ni;ZHENG Ping;MA Ping;DAI Gui-dong;XU Qing-bin;Department of Pharmacology,Ningxia Medical University;Department of Cardiology,General Hospital of Ningxia Medical University;Department of Pharmaceutical Engineering,School of Chemical and Materials Engineering,Kaili University;

• 1:宁夏医科大学药学院药理学系
• 2:宁夏医科大学总医院心内科
• 3:凯里学院化学与材料工程学院制药工程系

摘要(Abstract)：

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。
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 SpragueDawley 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 8thday 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.

关键词(KeyWords)： 氧化苦参碱;异丙肾上腺素;慢性心力衰竭;ADMA;PRMT1;DDAH2
oxymatrine;isoproterenol;chronic heart failure;ADMA;PRMT1;DDAH2

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81060024)

作者(Authors): 王洋;徐烨华;熊爱琴;袁娅妮;郑萍;马萍;戴贵东;徐清斌;
WANG Yang;XU Ye-hua;XIONG Ai-qin;YUAN Ya-ni;ZHENG Ping;MA Ping;DAI Gui-dong;XU Qing-bin;Department of Pharmacology,Ningxia Medical University;Department of Cardiology,General Hospital of Ningxia Medical University;Department of Pharmaceutical Engineering,School of Chemical and Materials Engineering,Kaili University;

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