Abstract
OBJECTIVE:To study tanshinone ⅡA inhibiting the proliferation and migration induced by homocysteine(Hcy)of rat aortic vascular smooth muscle cells(VSMCs)and its signal pathway. METHODS:VSMCs were selected for the following ex-periments. In order to validate TanshinoneⅡA inhibiting the proliferation and migration induced by Hcy of VSMCs,VSMCs were di-vided into control group,Hcy group(1 000μmol/L),TanshinoneⅡA low-dose,medium-dose and high-dose groups(5,10,20 µg/L). In mechanism study test,VSMCs were divided into control group,TanshinoneⅡA group(20 µg/L),rapamycin group(20 nmol/L), MHY1485 group(10μmol/L),TanshinoneⅡA+rapamycin group(TanshinoneⅡA,20 µg/L+rapamycin,20 nmol/L),TanshinoneⅡA+MHY1485 group (TanshinoneⅡA,20 µg/L+MHY1485,10 μmol/L). In validation test of P70S6K and p-P70S6K pathway expres-sion,rapamycin and MHY1485 were used for inhibitory test and activation test,respectively. The proliferation of VSMCs was de-termined by ELIASA,and Transwell chambers and wound healing test were employed to test the migratory ability of VSMCs. West-ern blotting were used to investigate the expressions of P21,P27,MMP-2,MMP-9,P70S6K and p-P70S6K in VSMCs. RE-SULTS:In validation test,compared with control group,24,48 h absorbance,migration area,the number of VSMCs penetration and the expression of MMP-2,MMP-9 and p-P70S6K increased significantly,while the expression of P21 and P27 decreased sig-nificantly(P<0.01). Compared with Hcy group,48 h absorbance of TanshinoneⅡA low-dose group,24,48 h absorbance and the expression of MMP-2 of TanshinoneⅡA medium-dose and high-dose groups,migration area,the number of VSMCs penetration, the expression of MMP-9 and p-P70S6K in low-dose,medium-dose and high-dose groups all decreased significantly;the expres-sion of P21 and P27 increased significantly in TanshinoneⅡA medium-dose and high-dose groups(P<0.01);there was no statisti-rapamycin group,while 24,48 h absorbance increased significantly in MHY1485 group(P<0.01). Compared with TanshinoneⅡA group,24,48 h absorbance decreased significantly in TanshinoneⅡA+rapamycin group,while 12,24,48 h absorbance,migration area and the number of VSMCs penetration increased significantly in TanshinoneⅡA+MHY1485 group (P<0.01). In inhibitory test,compared with control group,the expression of p-P70S6K decreased significantly in TanshinoneⅡA group (P<0.01);com-pared with TanshinoneⅡA group,the expression of p-P70S6K decreased significantly in rapamycin group and TanshinoneⅡA+rapa-mycin group(P<0.01);in activation test,the expression of p-P70S6K decreased significantly in TanshinoneⅡA group(P<0.01), compared with TanshinoneⅡA group,the expression of p-P70S6K increased significantly in MHY1485,TanshinoneⅡA+MHY1485 group (P<0.01). CONCLUSIONS:TanshinoneⅡA can inhibit the proliferation and migration of VSMCs by suppressing mTOR/P70S6K signal pathway.关键词
血管平滑肌细胞/丹参酮ⅡA/雷帕霉素受体/P70S6K/增殖/迁移Key words
Vascular smooth muscle cells/TanshinoneⅡA/mTOR/P70S6K/Proliferation/Migration分类
医药卫生
