p38丝裂素活化蛋白激酶介导自发性高血压大鼠血管平滑肌细胞增殖  

p38 mitogen-activated Protein Kinase in Vascular Smooth Muscle Cells Proliferation in SHR

作　　者：许柳青[1] 叶琼[1] 许昌声[1] 王华军[1] 吴可贵[1] 

机构地区：[1]福建医科大学附属第一医院,福建福州350005

出　　处：《中华高血压杂志》2007年第9期759-763,共5页Chinese Journal of Hypertension

摘　　要：目的研究p38丝裂素活化蛋白激酶(p38MAPK)信号传导通路在血管紧张素Ⅱ(AngⅡ)与血小板源性生长因子-BB(PDGF-BB)诱导的自发性高血压大鼠(SHR)血管平滑肌细胞(VSMC)增殖中的作用。方法本实验采用体外培养SHR胸主动脉平滑肌细胞,用3H-胸腺嘧啶核苷([3H]-TdR)掺入法测定细胞增殖状况。用特异性的Phospho-p38MAPK抗体的蛋白免疫印迹法(Westernblot)检测p38MAPK的活性。结果1)AngⅡ、PDGF成剂量依赖性促进SHR血管平滑肌细胞[3H]-TdR掺入率,当AngⅡ为10-7mol/L、PDGF为10ng/L时,[3H]-TdR掺入率显著增加[AngⅡ组:(11588±1322)比对照组(2546±207)计数/min;PDGF:(5279±391)比对照组(2587±230)计数/min,P<0.05]。p38MAPK选择性阻断剂SB202190(10-9～10-7mol/L)呈浓度依赖性地降低AngⅡ、PDGF诱导的VSMC增殖活度。2)AngⅡ、PDGF对p38MAPK的磷酸化均有显著增强作用,此作用同样被SB202190抑制。3者作用都呈剂量依赖性。结论AngⅡ、PDGF能激活SHR血管平滑肌细胞的p38MAPK发生磷酸化,进而导致血管平滑肌细胞增殖。Objective To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） pathway in the proliferation of SHR vascular smooth muscle cells（VSMC） induced by angiotensin Ⅱ （Ang Ⅱ ） and plateletderived growth factor-BB（PDGF-BB）. Methods VSMC were obtained from SHR thoracic aorta. DNA synthesis was quantified by measuring [^3 H]-thymidine incorporation. The p38MAPK activity was evaluated by immunobloting technique with phospho-p38MAPK antibody. Results 1） Ang Ⅱ （10^-8-10^-6 mol/L）, PDGF（3- 30 ng/L） dose-dependently increased the proliferation activity of VSMC （^3 H]-TdR incorporation）. Ang Ⅱ （10^-7 mol/L） or PDGF（10 ng/L） significantly increased [^3 H]-TdR incorporation rate in VSMCs（Ang Ⅱ ：11 588 ±1322 vs control 2546±207 counts/min, P〈0.05; PDGF：5279±391 vs control 2587±230 counts/min, P〈0. 05）. Cocultured with SB202190（10^-9 - 10^-7 mol/L, a selective antagonist of p38MAPK, decreased the proliferation of VSMC stimulated by Ang Ⅱ （10^-7 mol/L） or PDGF（10 ng/L） in a dose-dependent manner（P〈0.05）. 2）Ang Ⅱ （10^-8 - 10^-6 mol/L）or PDGF（3-30 ng/L） induced phosphorylation of p38MAPK in a dosedependent manner which was inhibited by SB202190（10^-9 - 10^-7 mol/L）. Conclusion Ang Ⅱ or PDGF stimulated SHR VSMC proliferation might be mediated by the phosphorylation of p38MAPK.

关 键 词：P38丝裂素活化蛋白激酶 血管紧张素Ⅱ 血小板源性生长因子 细胞增殖 血管平滑肌细胞 

分 类 号：R544.1[医药卫生—心血管疾病]