钩藤碱和异钩藤碱抑制血管紧张素Ⅱ诱导血管平滑肌细胞增殖及相关机制  

Effect of rhynchophylline and isorhynchophylline on the proliferation of rat vascular smooth muscle cell induced by angiotensin Ⅱ

作　　者：李运伦[1] 

机构地区：[1]山东中医药大学附属医院心内科,山东济南250011

出　　处：《中国药理学通报》2008年第1期53-58,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题(No30300466);山东省优秀中青年科学家奖励基金资助课题(No03BS024)

摘　　要：目的探讨钩藤碱和异钩藤碱对血管紧张素Ⅱ诱导的血管平滑肌细胞增殖的抑制效应及相关机制。方法建立血管紧张素Ⅱ诱导血管平滑肌细胞增殖模型,通过四甲基偶氮唑盐比色法、流式细胞术和逆转录聚合酶链反应观察钩藤碱和异钩藤碱对其增殖活性、细胞周期、细胞膜AT1R蛋白表达、信号转导通路NF-κB和Stat3蛋白表达、原癌基因c-Myc和c-Fos蛋白表达与mRNA转录的影响。结果血管紧张素Ⅱ明显刺激血管平滑肌细胞增殖,钩藤碱和异钩藤碱呈剂量依赖性抑制血管紧张素Ⅱ诱导的血管平滑肌细胞增殖;在钩藤碱和异钩藤碱干预下,血管平滑肌细胞处于G0/G1期的细胞数明显增多,S期的细胞数明显减少,c-Myc、c-Fos、AT1R、NF-κB、Stat3的蛋白表达以及c-MycmRNA和c-FosmRNA转录也明显降低。结论钩藤碱和异钩藤碱对血管紧张素Ⅱ诱导血管平滑肌细胞增殖有明显抑制效应,其机制与阻滞血管平滑肌细胞G0/G1期向S期转化以及下调AT1R、NF-κB、Stat3、c-Myc、c-Fos蛋白的表达以及c-MycmR-NA和c-FosmRNA转录有关。Aim To study the effect of rhynchophylline and isorhynchophylline on the proliferation of rat vascular smooth muscle cell （VSMCs） induced by angiotensin Ⅱ （ Ang Ⅱ ） and discuss it＇s mechanism. Methods A cell proliferating model of VSMC induced by Ang Ⅱ was established. The proliferative activity of VSMC with rhynchophylline and isorhynchophylline was analyzed by MTF method. The effect of rhynchophylline and isorhynchophylline on cell cycle of VSMC was observed by flow cytometry. The effect of rhynchophylline and isorhynchophylline on protein of AT~ R gene, NF- κB gene, Stat3 gene, c-Myc gene and c-Fos gene in VSMCs was observed by flow cytometry. The effect of rhynchophylline and isorhynchophylline on c-Myc mR- NA and c-Fos mRNA in VSMCs was observed by RTPCR. Results The proliferation of VSMC induced by Ang Ⅱ stimulation was inhibited by rhynchophylline and isorhynchophylline, and the cell numbers of G0/Gl phase were increased and those of S phase were de-creased markedly. At the same time, high expression of the protein of c-Myc gene,c-Fos gene, AT1R gene, NF-κB gene and stat3 gene stimulated by Ang Ⅱ could be inhibited by rhynchophylline and isorhynchophylline significantly, and high expression of c-Myc gene mR- NA and c-Fos gene mRNA stimulated by Ang Ⅱ could also be inhibited by rhynchophylline and isorhyncho- phylline significantly. Conclusions The proliferation of VSMCs induced by Ang Ⅱ can be inhibited by rhynchophylline and isorhynchophylline. The mechanisms are related to preventing VSMCs from G0/G1 phase entering S phase , and down regulating the expression of protein of AT1R gene, NF-κB gene,Stat3 gene, c-Myc gene and c-Fos gene. In addition, c-Myc gene mRNA and c-Fos gene mRNA expression are down regulated as well.

关 键 词：钩藤碱 异钩藤碱 血管平滑肌细胞 增殖 信号转导通路 血管紧张素Ⅱ 

分 类 号：R-332[医药卫生] R284.1