血管紧张素Ⅱ诱导自发性高血压大鼠血管外膜成纤维细胞迁移活性涉及P38 MAPK  

P38 MAPK was involved in angiotensin-induced migratory potential of adventitial fibroblasts from spontaneously hypertensive rat

作　　者：李莉[1] 高平进[2] 沈伟利[2] 刘建军[2] 朱鼎良[2] 

机构地区：[1]杭州市第二人民医院心内科,310015 [2]上海第二医科大学附属瑞金医院上海市高血压研究所

出　　处：《中华心血管病杂志》2005年第6期557-560,共4页Chinese Journal of Cardiology

基　　金：国家重点基础研究发展规划973(G2000056904)

摘　　要：目的研究血管紧张素Ⅱ(AngⅡ)诱导自发性高血压大鼠(SHR)血管外膜成纤维细胞迁移活性的变化及该过程是否涉及P38MAPK信号途径。方法用TranswellChamber观察AngⅡ诱导的血管外膜成纤维细胞的迁移活性,及AT1受体拮抗剂氯沙坦、P38MAPK特异性的抑制剂SB202190对AngⅡ诱导的迁移活性的影响。进一步用免疫印迹技术观察AngⅡ诱导后P38MAPK的磷酸化,及氯沙坦、SB202190对P38MAPK磷酸化的影响。结果AngⅡ诱导SHR大鼠血管外膜成纤维细胞迁移活性较WKY大鼠显著增高,且呈剂量依赖性。氯沙坦及SB202190能抑制AngⅡ诱导的迁移活性。AngⅡ诱导SHR外膜成纤维细胞P38MAPK的磷酸化,呈剂量和时间依赖性;该作用能够被氯沙坦、SB202190抑制。结论AngⅡ诱导SHR大鼠血管外膜成纤维细胞迁移活性增强,该过程涉及P38MAPK信号途径。Objective To test whether P38 MAPK is involved in angiotensin Ⅱ (Ang Ⅱ)-enhanced migration potential of adventitial fibroblasts (AFs) from spontaneously hypertensive rat (SHR).Methods Migratory potential was estimated by transwell chamber in vitro. Activation of P38 MAPK pathway was determined with phosphospecfic antibodies by immunoblotting.Results AngⅡ induced migration of SHR-AFs was markedly increased in a dose-dependent manner when compared with WKY-AFs. Addition of the AngⅡ receptor type-1 (AT1-R) antagonist Losartan and P38 MAPK inhibitor SB202190 suppressed AngⅡ-induced migration of SHR-AFs. AngⅡ could induce P38 MAPK phosphorylation in SHR-AFs in a time-and dose-dependent manner. Phosphorylation of P38 MAPK was suppressed by Losartan and SB202190.Conclusion This study indicated that AngⅡ-induced migration involves P38 MAPK pathway via AT1 receptor in aortic adventitial fibroblasts from SHR.

关 键 词：血管紧张素Ⅱ 自发性高血压 大鼠 血管外膜 成纤维细胞 迁移活性 P38MAPK 

分 类 号：R544.1[医药卫生—心血管疾病]