血清和糖皮质激素诱导的蛋白激酶1介导外膜成纤维细胞表型转化  

Serum/glucocorticoid regulated kinase 1 promotes adventitial fibroblasts phenotypic transformation

作　　者：杜雅楠[1] 许建忠[1] 张宝丽[1] 韩卫青[2] 高平进[1] 唐晓峰[1] Du Yanan, Xu Jianzhong, Zhang Baoli, Han Weiqing, Gao Pingjin, Tang Xiaofeng(Department of Hypertension ,Ruij in Hospital, Shanghai J iaotong University School of Medicine, Shanghai Institute of Hypertension, Shanghai 200025, Chin)

机构地区：[1]上海交通大学医学院附属瑞金医院高血压科,200025 [2]上海市高血压研究所

出　　处：《中华老年心脑血管病杂志》2018年第3期294-297,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81100184;81230071);上海市自然科学基金(17ZR1423700);上海市浦江人才计划(14PJ1406400);上海市卫生和计划生育委员会科研课题(201540037;201440023);上海交通大学医学院科技基金(14XJ10042)

摘　　要：目的探讨血清和糖皮质激素诱导的蛋白激酶1(SGK1)是否参与血管外膜成纤维细胞(AF)表型转化。方法选取雄性SD大鼠,组织切块法培养胸主动脉AF,将未用转化生长因子β1(TGF-β1)刺激的AF分别作为空白组、对照1和2组,用2.5、5.0、10.0和15.0ng/ml TGF-β1诱导AF依次为A、B、C和D组;分别用50μmol/L的EMD638683和SB203580预处理细胞为抑制剂1和2组;用5ng/ml TGF-β1刺激细胞分别为刺激1和2组。Western blot检测SGK1、α平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原蛋白相对表达量。结果与空白组比较,A、B和C组SGK1表达显著增加(P<0.05),B组SGK1表达量最高;B、C和D组α-SMA表达显著增加(P<0.05),C组α-SMA表达量最高(P<0.05)。与对照1组比较,刺激1组细胞α-SMA和Ⅰ型胶原蛋白表达明显升高(P<0.05),与刺激1组比较,抑制剂1组细胞α-SMA和Ⅰ型胶原蛋白表达显著降低(P<0.05);与对照2组比较,刺激2组细胞SGK1表达明显升高(P<0.05),与刺激2组比较,抑制剂2组细胞SGK1表达显著降低(P<0.05)。结论 SGK1通过p38促分裂素原活化蛋白激酶参与TGF-β1诱导的血管AF表型转化,参与血管的病理性重构。Objective To study whether SGK1 is involved in the phenotypic transformation in adventitial fibroblasts（AF）.Methods Vascular AF were separated from the thoracic aortas of SD rats.The AF not stimulated with TGF-β1 were divided into blank group,control group 1 and control group 2.The AF induced with 2.5,5.0,10.0 and 15.0 ng/ml TGF-β1 were divided into groups A-D.The AF pretreated with 50μmol/l EMD638683 and SB203580 were divided into inhibitor group 1 and inhibitor group 2.The AF stimulated with 5 ng/ml TGF-β1 were divided into stimulation group 1 and stimulation group 2.The expression of SGK1,α-SMA and collagen I was detected by Western blot.Results The expression of SGK1 was significantly higher in groups AC than in blank group.The expression ofα-SMA was significantly higher in groups B-D than in controlgroup（P0.05）.Theα-SMA and collage I expression levels were significantly higher in stimulation group 1 than in control group 1,and were significantly lower in inhibitor group 1 than in stimulation group 1（P0.05）.The SGK1 expression level was significantly higher in stimulation group 2 than in control group 2 and was significantly lower in inhibitor group 2 than in stimulation group 2（P0.05）.Conclusion SGK1 participates in TGF-β1-induced phenotypic transformation via p38 MAPK and is thus involved in vascular remodeling.

关 键 词：糖皮质激素类 蛋白激酶类 转化生长因子Β1 胶原Ⅰ型 

分 类 号：R543.5[医药卫生—心血管疾病]