【摘要】 目的:研究Probucol抑制ox-LDL诱导RASMCs增殖与信号蛋白分子ERK1/2、MKP-1、HO-1和Trx-1表达之间的关系。方法:采用MTT、流式细胞术和Western blotting观察ox-LDL刺激条件下probucol对细胞周期、细胞增殖和凋亡、ERK1/2、MKP-1、HO-1和Trx-1表达的影响。结果:(1)Probucol抑制ox-LDL刺激RASMCs增殖:100μmol/Lprobucol+35mg/Lox-LDL组与35mg/Lox-LDL组比较,A值下降了34.9%(P<0.01);(2)Probucol通过使RASMCs停滞在G0/G1期和诱导细胞凋亡2种方式抑制ox-LDL刺激细胞增殖。(3)ox-LDL显著抑制MKP-1的蛋白表达,与对照组比较下降了60.0%(P<0.01),同时使p-ERK1/2表达增加了34.7%;Probucol使MKP-1蛋白表达显著增加2倍,p-ERK1/2表达降低了15.7%(P<0.01);(4)35mg/Lox-LDL使细胞内Trx-1蛋白表达下降28.9%(P<0.05),HO-1蛋白表达轻度增加(P<0.05)。与ox-LDL组比较,probucol使Trx-1蛋白表达增加了91.6%(P<0.01),HO-1表达增加31.9%(P<0.01)。结论:Probucol通过增强MKP-1和HO-1蛋白表达、抑制细胞周期运转和诱导细胞凋亡的机制抑制RASMCs增殖。更多还原

【Abstract】 AIM:To investigate the relationships between antiproliferative mechanisms of probucol and protein expressions of signaling molecules ERK1/2,MKP-1,HO-1 and Trx-1 in rat aortic smooth muscle cells (RASMCs) stimulated with ox-LDL. METHODS:The effects of probucol on cell cycle,cell proliferation and the expressions of ERK1/2,MKP-1,HO-1 and Trx-1 in the presence of ox-LDL were observed by means of MTT test,FCM and Western blotting. RESULTS:(1) Probucol significantly inhibited the proliferation of RASMCs stimulated with ox-LDL. A value in 100 μmol/L probucol+35 mg/L ox-LDL group was reduced by 34.9% as compared to ox-LDL group (P<0.01). (2) Probucol protected against ox-LDL-induced RASMCs proliferation through inducing cell growth arrest at G0/G1 phase and cell apoptosis. (3) ox-LDL increased the expression of p-ERK1/2 by 34.7% (P<0.01) and decreased MKP-1 by 60.0% (P<0.01),respectively,as compared to control. Probucol attenuated the increase in ox-LDL-stimulated p-ERK1/2 level by 15.7%,but increased MKP-1 expression by 2 times (P<0.01). (4)ox-LDL at concentration of 35 mg/L decreased the intracellular Trx-1 expression by 28.9% (P<0.05),and slightly increased the level of HO-1 expression as compared to control (P<0.05). Probucol enhanced the expression of Trx-1 by 91.6% (P<0.01) and HO-1 by 31.9% (P<0.01),respectively as compared to ox-LDL group. CONCLUSION:Probucol inhibits ox-LDL-stimulated the proliferation of RASMCs through increases in MKP-1/HO-1 expression,suppression of cell cycle progression and induction of cell apoptosis.更多还原