血管紧张素Ⅱ刺激血管平滑肌细胞表达TSLP及信号通路研究

Expression of thymic stromal lymphopoietin in vascular smooth muscle cells induced by angiotensin Ⅱ and the possible signaling pathway

目的:观察血管紧张素Ⅱ(AngⅡ)是否可以刺激血管平滑肌细胞(VSMC)表达胸腺基质淋巴细胞生成素(TSLP),探讨核因子-κB(NF-κB)信号途径在这一过程中的作用。方法:原代培养VSMC,分别用AngⅡ及AngⅡ联合NF-κB特异性抑制剂PDTC干预。采用免疫组织化学染色检测胞浆中TSLP的表达,用ELISA法检测细胞培养上清液中TSLP的浓度,用电泳迁移率实验(EMSA)检测NF-κB的结合活性。结果:正常未经处理的VSMC几乎不表达TSLP,经AngⅡ刺激后胞浆及上清中的TSLP明显增加,并有浓度和时间依赖性,经PDTC预处理后TSLP表达量明显减少。相同条件下AngⅡ可激活VSMC的NF-κB信号通路,PDTC可抑制这一过程。结论:AngⅡ能够刺激血管平滑肌细胞表达TSLP,其作用机制可能是上调了NF-κB的结合活性。

Objective：To study the expression of thymic stromal lymphopoietin （TSLP） in VSMC induced by angiotensin Ⅱ （ Ang Ⅱ ） and the dependent signaling pathway. Methods： Primary rat VSMC were cultured and identified. Cells were then randomly divided into control group,Ang Ⅱ stimulated group and combination of Ang Ⅱ and PDTC treated group. Expression of TSLP in VSMC was detected by immunohistochemistry. Levels of TSLP in the supernatant were assessed by ELISA, and then the NF-KB DNA binding activity was determined by EMSA. Results： Primary vSMC express few TSLP. Incubation of VSMC with Ang Ⅱ resulted in activation of NF-KB and a significant increase of TSLP protein expression. VSMC pretreated with PDTC showed marked inactivation of NF-KB and meanwhile a significant decrease in TSLP release on Ang II treatment. Conclusion ： Ang Ⅱ can induce expression of TSLP in VSMC, which may be regulated by NF-KB signaling pathway. This process may play a critical role in the development of atherosclerosis.