目的：验证瑞舒伐他汀是否具有抑制同型半胱氨酸（Hcy）诱导的大鼠血管平滑肌细胞（VSMCs）表型转化的作用及其可能的信号通路。方法 SD大鼠主动脉VSMCs原代细胞培养鉴定，取4～7代细胞用于实验。VSMCs分为空白组、100μmol／L Hcy干预组、Hcy＋瑞舒伐他汀干预组、Hcy＋雷帕霉素干预组共4组。MTT 法测各组VSMCs的增殖；划痕法和Transwell法测各组VSMCs的迁移；ICC法观察各组VSMCs的细胞形态；Western blot 检测各组VSMCs中SM‐actin、SM‐M HC、calponin、OPN、p‐P70S6K1的表达。结果相比于空白组，Hcy组 VSMCs增殖和迁移增加；细胞形态变圆；SM‐MCH和calponin表达减少（P＜0．01）；OPN和p‐P70S6K1表达增加（P＜0．01）。相比于Hcy组，瑞舒伐他汀组和雷帕霉素组 VSMCs增殖和迁移减少，细胞形态变的细长，SM‐M HC和calponin表达增加（ P＜0．01）；OPN和p‐P70S6K1表达减少（P＜0．01）。结论 Hcy可以促进VSMCs表型转化，瑞舒伐他汀可以抑制 Hcy的这一作用，其机制可能是通过抑制mTOR／P70S6K1信号通路实现的。%ABSTRACT:Objective To verify whether rosuvastatin can inhibit homocysteine (Hcy)‐induced rat aortic vascular smooth muscle cell (VSMC ) phenotype transformation and its potential mechanism .Methods The primary culture and identification of rat VSMCs were conducted , using VSMCs in passage4‐7 for the following experiments .The VSMCs were divided into 4 groups:control group ,Hcy (100μmol/L) group ,Hcy+ rosuvastatin group ,and Hcy+ rapamycin group .MTT was used to investigate the proliferation of VSMCs .Transwell chambers and wound healing were employed to test the migration ability of VSMCs . ICC was used to detect the VSMCs'morphology .Western blotting was used to investigate the expressions of SM‐actin ,SM‐MHC ,calponin ,OPN ,and p‐P70S6K1 in VSMCs of each group .Results Compared with those in control group , the proliferation and migration ability of VSMCs were significantly increased in Hcy modulation group (P< 0 .01) .The expressions of SM‐MCH and calponin increased but those of OPN and p‐P70S6K1 decreased in Hcy group compared with control group (P<0 .01) .The expression of SM‐actin did not significantly differ between the groups .Compared with those in Hcy modulation group , the proliferation and migration ability of VSMCs were significantly decreased in rosuvastatin and rapamycin groups ( P<0 .01) .The expressions of SM‐MCH and calponin increased while OPN and p‐P70S6K1 expressions decreased in rosuvastatin and rapamycin groups compared with Hcy group ( P< 0 .01 ) . Conclusion Hcy can induce the dedifferentiation of VSMCs ,and rosuvastatin can inhibit this effect of Hcy .Its potential mechanism may be realized via the mTOR/P70S6K1 signal pathway .
展开▼
