小白菊内酯抑制胎牛血清诱导的大鼠血管平滑肌细胞增殖及信号转导机理

Parthenolide inhibits fetal bovine serum induced proliferation of vascular smooth muscle cells and the mechanism of signal transduction

目的 探讨小白菊内酯的抗动脉粥样硬化机理与IκBα ,环氧合酶 2 (COX 2 ) ,p2 1,p2 7蛋白表达的关系。方法 培养大鼠胸主动脉血管平滑肌细胞(VSMC) ,Western印迹杂交法检测IκBα ,COX 2 ,p2 1,p2 7蛋白表达 ,流式细胞仪检测VSMC周期情况 ,[3H ]TdR参入测定VSMC的DNA合成。结果小白菊内酯 (30 μmol·L- 1)以时间依赖关系上调IκBα ,p2 1,p2 7蛋白表达和以时间依赖关系抑制COX 2蛋白表达 ,10～ 30 μmol·L- 1以剂量依赖关系使VSMC周期中的G0 /G1期细胞比例明显增多 ,S期细胞比例显著减少 ,同时抑制VSMC的 [3H]TdR参入。结论 ①小白菊内酯可能通过上调IκBα蛋白表达抑制核因子 κB活性 ,从而抑制COX 2蛋白表达 ,通过抑制COX 2蛋白表达来抑制VSMC增殖 ;②小白菊内酯可能通过上调调控G1 S周期转换的p2 1,p2 7蛋白来抑制VSMC增殖。

AIM To investigate the relationship between the mechanism of inhibition of parthenolide on the atherosclerosis and the protein expression of IκBα, cyclooxygenase 2(COX 2), p21, p27. METHODS Vascular smooth muscle cells were cultured, the protein level of IκBα, COX 2, p21, p27 was measured by Western blot method, cell cycle was examined with flow cytometry, the DNA synthesis was determined by TdR incorporation. RESULTS Parthenolide increased protein level of IκBα, p21, p27 and inhibited protein level of COX 2 in a time dependent manner. Flow cytometric DNA analysis revealed that parthenolide increased significantly G 0/G 1 phase of VSMC and decreased of S phase of VSMC in a dose dependent manner. Parthenolide inhibited TdR incorporation in a dose dependent manner. CONCLUSION ①Parthenolide may inhibit the activity of NF κB by up regulating the expression of IκBα, inhibit the expression of COX 2 by inhibiting the activity of NF κB and inhibit proliferation of VSMC by inhibiting the expression of COX 2. ②Parthenolide may inhibit proliferation of VSMC by increasing expression of G 1/S transfer related protein p21, p27.