小檗碱对Ang Ⅳ诱导血管平滑肌细胞增殖的影响  

Inhibitory effects of berberine on proliferation of vascular smooth muscle cells induced by angiotensin Ⅳ

作　　者：王全华[1] 陈加飞[1] 王平 吴芹[3] 蒋青松[1] 

机构地区：[1]重庆医科大学药理学教研室,400016 [2]重庆科瑞制药公司,400060 [3]遵义医学院药理教研室,贵州遵义563003

出　　处：《重庆医学》2012年第21期2131-2133,共3页Chongqing medicine

基　　金：国家自然科学基金资助项目(81100905);重庆市自然科学基金资助项目(2010BB5108)

摘　　要：目的研究小檗碱(BBR)对血管紧张素Ⅳ(AngⅣ)诱导大鼠血管平滑肌细胞(VSMCs)增殖的作用及机制。方法体外培养大鼠胸主动脉VSMCs,采用BCA法测细胞总蛋白含量和MTT法观察VSMCs的增殖;Real-time RT-PCR方法检测内皮型一氧化氮合酶(eNOS)mRNA的表达;比色法和硝酸还原法分别检测细胞培养液中一氧化氮合酶(NOS)活性和一氧化氮(NO)含量。结果 BBR(10、30、100μmol/L)呈浓度依赖性地抑制AngⅣ(0.1nmol/L)诱导的VSMCs的增殖和蛋白含量的增加(P<0.05);并上调AngⅣ所致eNOS mRNA表达的减少(P<0.05),同时升高AngⅣ降低的NOS活性和NO浓度(P<0.05)。L-精氨酸也有类似作用(P<0.05),而NG-硝基-L-精氨酸甲酯可以抵消BBR和L-精氨酸的上述作用(P<0.05)。结论 BBR可抑制AngⅣ诱导的VSMCs增殖,该作用可能与其激活eNOS mRNA的表达,增加NOS活性,促进NO释放有关。Objective To investigate the effects of berberine on the proliferation of vascular smooth muscle cells （VSMCs） in- duced by angiotensin Ⅳ（Ang Ⅳ）,and explore the possible mechanisms related to nitric oxide （NO）. Methods Primary VSMCs were cultured by tissue explant method. Cell proliferation were measured by MTT and total protein contents assays to observe the effects of berberine （10,30,100 μmol/L） on VSMCs proliferation induced by Ang Ⅳ （0.1 nmol/L）. The expression of endothelial NO synthase （NOS） mRNA was determined by real time RT PCR method. The NOS activity and NO concentration in culture media were assayed by speetrophotometry and nitrate reduction methods, respectively. Results Berberine remarkably inhibited VSMCs proliferation induced by Ang Ⅳin a dose-dependent manner（P〈0.05） ,and increased the activity of NOS and the contents of NO in cultured cells（P〈0.05）. Furthermore, berberine up-regulated the expression level of endothelial NOS mRNA（P〈0.05）. L arginine had a similar effect to berberine（P〈0.05）. NG-nitro-L-arginine methyl ester,NOS inhibitor,could abolish above effects of both berberine and L arginine（P〈0.05）. Conclusion Berberine obviously attenuated the cultured VSMCs proliferation induced by Ang Ⅳ. The mechanisms are,at least partly,due to up-regulating the expression of eNOS,then increasing NOS activity,and pro- moting the synthesis and release of NO.

关 键 词：小檗碱 血管平滑肌细胞 增殖 血管紧张素Ⅳ 一氧化氮 

分 类 号：R285[医药卫生—中药学]