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  

Protective effect of oxymatrine on chronic heart failure and ADMA metabolism pathway in isoproterenol-induced chronic heart failure in rats

作　　者：王洋[1] 徐烨华 熊爱琴 袁娅妮 郑萍[1] 马萍[2] 戴贵东[3] 徐清斌[2] 

机构地区：[1]宁夏医科大学药学院药理学系,宁夏银川750004 [2]宁夏医科大学总医院心内科,宁夏银川750004 [3]凯里学院化学与材料工程学院制药工程系,贵州凯里556011

出　　处：《中国中药杂志》2014年第3期471-477,共7页China Journal of Chinese Materia Medica

基　　金：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。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 methyhransferases 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：氧化苦参碱 异丙肾上腺素 慢性心力衰竭 ADMA PRMT1 DDAH2 

分 类 号：R285.5[医药卫生—中药学]