乙酰水杨酸姜黄素酯对血管紧张素II诱导的血管平滑肌细胞增殖的影响及相关机制

摘要

目的 探讨乙酰水杨酸姜黄素酯(curcumin acetylsalicylate,CA)对血管紧张素II(Angiotensin II,AngII)诱导的血管平滑肌细胞(vascular smooth muscle cells,VSMC)增殖的抑制作用及其相关机制.方法 建立AngII诱导的VSMC增殖模型.采用MTT法、流式细胞术观察CA干预对细胞活力和周期的影响.Western blot检测其对第10号染色体同源缺失性磷酸酶张力蛋白(phosphatase and tensin homolog deleted on chromosome ten,PTEN)、磷酸化AKT(p-AKT)、AKT蛋白表达的影响.结果 1、3、10μmol/L CA可以显著抑制AngII诱导的细胞活力,其中3μmol/L为最佳浓度(P<0.05).在CA的干预下,与AngII组比较,流式细胞术显示VSMC G0/G1期细胞数量明显增加,S期明显减少;Western blot显示其可以促进PTEN蛋白表达,从而抑制AKT激活(P<0.05).结论 CA可以抑制AngII诱导的VSMC增殖,其机制与阻滞VSMC G0/G1期向S期转化,以及调节PTEN/AKT信号通路有关.%Objective To investigate the effect and mechanism of curcumin acetylsalicylate (CA) on Angiotensin II (AngII) induced proliferation in vascular smooth muscle cells (VSMC). Methods VSMC proliferation model was induced by AngI-I. Flow cytometry was used to observe the effect of CA on cell proliferation and cycle. The expressions of PTEN, p-AKT and AKT was detected by Western blot. Results 1, 3, 10 μmol/L CA led to a significant inhibition of Ang II-induced proliferation of VSMCs and 3 μmol/L CA was proved to be an optimal inhibitory concentration (P<0.05). Flow cytometry showed that the number of cells in G0/G1 phase increased significantly and the number of S phase decreased significantly by the interven-tion of CA. Western blot showed that it could promote the expression of PTEN protein and inhibit the activation of AKT (P<0.05). Conclusion CA can obviously inhibit the VSMC proliferation induced by AngII, and its mechanism is related to the inhi-bition of transformation from G0/G1 phase to S phase and the regulation of PTEN/Akt signaling pathway.