MAPK信号通路介导血管紧张素Ⅱ对人外周血早期内皮祖细胞的功能调节  

MAPK pathway mediated angiotensin Ⅱ regulates the function of early endothelial progenitor ceils

作　　者：张浩[1] 孙文文[1] 施良[2] 王翠平[3] 蔡华忠[1] 毛学群[4] 宋迎春[1] 尹江宁[1] 任国庆[1] 

机构地区：[1]江苏大学附属医院急诊科,江苏镇江212001 [2]江苏大学附属医院核医学科,江苏镇江212001 [3]江苏大学附属医院心内科,江苏镇江212001 [4]江苏大学附属医院介入放射科,江苏镇江212001

出　　处：《中国急救医学》2015年第12期1134-1138,I0010,共6页Chinese Journal of Critical Care Medicine

基　　金：基金项目：国家自然科学基金青年项目（NSFC81400269）;镇江市社会发展科技支撑项目（SH2014033）;江苏大学临床医学专项基金（JDLCZX012）

摘　　要：目的探讨血管紧张素Ⅱ（AngⅡ）对内皮祖细胞（EPCs）增殖、迁移、黏附功能的影响及MAPK信号通路在其中的作用。方法取健康成人外周血分离、培养出EPCs并鉴定。以不同浓度AngⅡ（0．1、1、10、100μmol／L）干预，得出最佳浓度用于后续干预实验。分组：对照组、AngⅡ组、JNK抑制剂SP600125＋AngⅡ组、ERKI／2抑制剂A6355＋AngII组和p38抑制剂PDl69318＋AngⅡ组。检测各组EPCs的增殖、迁移、黏附能力。结果AngII对EPCs增值能力无显著影响；AngⅡ可促进EPCs的迁移、黏附功能，在1μmol／L时达到最大效果。AngII对EPCs迁移功能的促进作用能被JNK抑制剂SP600125（P〈0．01）、ERK1／2抑制剂A6355（P〈0．01）和p38抑制剂PD169318（P〈0．05）抑制。其中，ERK1／2抑制剂A6355的抑制作用最显著。AnsⅡ对EPCs黏附功能的促进作用可被JNK抑制剂SP600125（P〈0．05）、ERK1／2抑制剂A6355（P〈0．01）和p38抑制剂PD169318（P〈0．05）抑制。结论AngⅡ可能通过激活MAPK信号通路促进EPCs的迁移、黏附功能。Objective To analyze the effects of angiotensin Ⅱ（Ang Ⅱ ） on the proliferation, migration and adhesion of endothelial progenitor cells （EPCs） and the role of MAPK pathway in this process. Methods EPCs were cultured in serum - free EBM - 2 medium for 24 h before incubation with various concentrations of Ang Ⅱ （0.1, 1, 10, 100 μmol/L） for 48h. EPCs proliferation, migration and adhesion capacities were measured. Choose the best concentrations of Ang Ⅱ. The adherent cells were coUected and divided into five groups randomly： control group, AngⅡ group, SP600125 ＋ AngⅡ , A6355 ＋ Ang Ⅱ and PD169318 ＋ Ang Ⅱ group. EPCs proliferation and migration and adhesion were assayed by MTT assay and modified Boyden chamber assay and cell counting respectively. Results Ang Ⅱ significantly increased the migration and adhesive ability of EPCs in a dose - dependent manner, maximum at 1μmol/L （P 〈0.05）, but has no effect on proliferative ability. The influence of AngⅡ on EPC migration capacities can be abolished by SP600125 （59.3 ±9.4 vs 113.6 ± 11.2, P 〈0. 01 ）, A6355（52.1 ± 10.4 vs 113.6 ± 11.2, P 〈0.01 ） and PD169318（64.6 ± 10.7 vs 113.6± 11. 2, P 〈 0.05 ）. Similarly, the adhesive capacities can be inhibited by SP600125 （41.3 ±10.2 vs 67.8 ± 10.3, P〈0.05）, A6355（39.6±12.4 vs 67.8 ±10.3, P 〈0.01）and PD169318（42. 1 ± 11.6 vs 67.8 ± 10. 3, P 〈 0. 05 ）. Conclusion Ang Ⅱ improves EPC migration and adhesion capacities through activating MAPK pathway.

关 键 词：内皮祖细胞(EPCs) 促分裂原活化蛋白激酶(MAPK) 血管紧张素Ⅱ(AngⅡ) 

分 类 号：R73-37[医药卫生—肿瘤]