JAK2/STAT3信号通路在阿托伐他汀抗大鼠血管平滑肌细胞增殖凋亡中的作用研究

目的探讨阿托伐他汀对大鼠血管平滑肌细胞(VSMCs)非调脂作用机制与转录信号传导子和激活子3(Stat3)信号传导通路的关系,明确其细胞内信号传导机制。方法分别将阿托伐他汀、酪氨酸激酶抑制剂AG490及二者联合作用于大鼠VSMCs,应用MTT法检测细胞增殖状态;流式细胞仪观察药物对细胞凋亡的影响,进一步用蛋白免疫印迹法(Western blot)检测药物作用前后 Stat3通路相关蛋白JAK2、STAT3、Cyclin D1、Bcl-2的表达及磷酸化活性。结果阿托伐他汀及AG490 都呈浓度依赖性方式抑制大鼠VSMCs增殖水平,促进其凋亡,二者联合应用则具协同作用。阿托伐他汀及AG490处理VSMCs后p-JAK2、p-Stat3、Cyclin D1、Bcl-2蛋白表达水平随作用时间延长而下降 (P<0．05),并且联合组蛋白表达水平较单独处理组相比有显著性差异(P<0．01)。结论阿托伐他汀对大鼠VSMCs非调脂作用机制与癌基因Star3信号通路高度相关,与酪氨酸激酶抑制剂AG490联合应用则具协同作用,可能通过作用于JAK2／Stat3下游靶基因Cyclin D1、Bcl-2影响其增殖及凋亡。

The Study on the Role of JAK2/Stat3 Signal Pathway in Treatment of Atorvastatin on Proliferation and Apoptosis of Vascular Smooth Muscle Cells of Rats

Objective The purpose of this study was conducted to investigate the role of Stat3 signal transduction pathway in treatment of Atorvastatin on proliferation and apoptosis of VSMCs. Methods VSMC of rats was treated with Atorvastatin and AG490. MTT assay and flow cytometry were used to measure the proliferation and apoptosis in cultured rat thoracic VSMC. the expression of p-JAK2, p-Stat3, Cyclin D1 and Bcl-2 were measured by western blot. Results Atorvastatin and AG490 inhibited the VSMCs proliferation and induced apoptosis in a dose.time-dependent manner and resulted in significant downregulation of Stat3, p-Stat3, CyclinDl ,Bcl-2. Conclusions Our results show that Atorvastatin may inhibit the proliferation and induce apoptosis of VSMCs and combined with AG490 create synergetic effects on VSMCs through Stat3 Signaling pathway, especially its downstream target gene CyclinDl and Bcl-2. This may be a new target of Atorvastatin effect on VSMCs.