3,3’双吲哚甲烷对凝血酶诱导的血管平滑肌细胞增殖的影响

Effects of 3,3'Diindolylmethane on proliferation of vascular smooth muscle cell induced by thrombin

目的研究3,3’双吲哚甲烷(3,3’Diindolylmethane,DIM)在体外对凝血酶诱导的血管平滑肌细胞(VSMC)增殖作用的影响及可能的分子机制。方法 WST-1方法检测VSMC增殖,5-溴-2’-脱氧尿苷(Brdu)掺入法检测细胞DNA合成,western blot检测p-Akt,p-GSK(糖原合酶激酶)-3β表达。结果凝血酶显著促进VSMC增殖和细胞DNA合成,而DIM呈剂量依赖性地抑制凝血酶诱导的VSMC增殖和DNA合成。对分子机制的研究发现DIM抑制Akt/GSK-3β磷酸化。结论 DIM抑制凝血酶诱导的VSMC增殖,这个作用可能与其抑制Akt/GSK-3β信号通路有关。

Objective To investigate the effects of 3,3＇Diindolylmethane（DIM） on proliferation of vascular smooth muscle cells（VSMC） induced by thrombin and the possible molecular mechanism.Methods Proliferation of VSMC was determined by WST-1 assay,DNA synthesis of VSMC was measured by 5-bromo-2＇-deoxyuridine（Brdu） incorporation.Western blot was carried out to evaluate phosphorylation of Akt and glycogen synthase kinase（GSK）-3β.Results DIM dose-dependently inhibited the thrombin-induced proliferation of VSMC without cell cytotoxicity.This effect was caused by inhibition of DNA synthesis demonstrated by Brdu incorporation.Mechanistically,DIM negatively modulated thrombin-induced phosphorylation of Akt/GSK-3β.Conclusions DIM can suppress the proliferation of VSMC induced by thrombin;These beneficial effects on VSMC were at least partly mediated by the inhibition of Akt/GSK-3β signal pathway.