GSK3β抑制剂TWS119对晚期糖基化终末产物诱导的人主动脉血管平滑肌细胞迁移的影响  

Effect of GSK3βinhibitor TWS119 on advanced glycation end products-induced migration of human aortic vascular smooth muscle cells

作　　者：袁罡 徐燕能 侯青春 王伟明 许凯强 王寓平 胥雄飞 刘勇 YUAN Gang;XU Yanneng;HOU Qingchun(Department of Intervention,Affiliated Traditional Chinese Medicine Hospital,Southwest Medical University,Luzhou 6A6000,CHINA)

机构地区：[1]西南医科大学附属中医医院介人诊疗科,四川泸州646000 [2]西南医科大学附属中医医院血管外科,四川泸州646000 [3]自贡市第四人民医院 [4]西南医科大学附属医院血管外科

出　　处：《江苏医药》2020年第5期473-477,F0002,共6页Jiangsu Medical Journal

基　　金：国家自然科学基金(81270358)。

摘　　要：目的探讨糖原合成酶激酶3β(GSK3β)选择性抑制剂TWS119对晚期糖基化终末产物(AGEs)诱导的人主动脉血管平滑肌细胞(HAVSMCs)迁移的作用及其可能机制。方法通过细胞划痕和Transwell实验筛选出最适促HAVSMCs迁移的AGEs浓度后,将HAVSMCs随机分为对照组、AGEs组、AGEs+TWS119组和AGEs+DMSO组。采用Transwell实验检测各组细胞迁移能力,细胞骨架染色激光共聚焦显微镜下观察纤维肌动蛋白表达,Western blot检测GSK3β、磷酸化GSK3β和MMP-2蛋白表达。结果AGEs组HAVSMCs迁移能力较对照组增强(P<0.01);与AGEs组相比,AGEs+TWS119组HAVSMCs迁移能力受到抑制,纤维肌动蛋白表达减弱,磷酸化GSK3β蛋白表达增加,MMP-2蛋白表达减少(P<0.01)。结论TWS119可能通过降低GSK3β活性和下调MMP-2蛋白表达,进而抑制AGEs诱导的HAVSMCs迁移。Objective To investigate the effect and underlying mechanism of glycogen synthase kinase 3β(GSK3β)selective inhibitor TWS119 on advanced glycation end products(AGEs)-induced migration of human aortic vascular smooth muscle cells(HAVSMCs).Methods After the optimal concentration of AGEs for the induction of cell migration was selected by cell scratch and Transwell assay,the HAVSMCs were equally divided into four groups of A(normal control),B(induced by AGEs 20 mg/L),C(pretreated with TWS11920μmol/L and then induced by AGEs 20 mg/L)and D(pretreated with DMSO and then induced by AGEs 20 mg/L).The cell migration was measured by Transwell assay.The expression of F-actin was observed under laser confocal microscope.The protein expressions of GSK3β,phosphorylated-GSK3βand MMP-2 were detected by Western blot.ResultsThe cell migration in group B was more than that in group A(P<0.01).Compared with group B,the cell migration was inhibited,F-actin expression was weakened,protein expression of phosphorylated-GSK3βwas increased,while protein expression of MMP-2 was decreased in group C(P<0.01).Conclusion TWS119 could inhibit AGEs-induced HAVSMCs migration probably via reducing the activation of GSK3βand downregulating the protein expression of MMP-2.

关 键 词：糖原合成酶激酶3Β TWS119 血管平滑肌细胞 迁移 

分 类 号：R654[医药卫生—外科学]