阻断p38信号转导通路对血管平滑肌细胞增殖和凋亡的影响

唐 梅; 王翠英; 李 敏

阻断p38信号转导通路对血管平滑肌细胞增殖和凋亡的影响

Molecular mechanism of p38 signaling pathway regulation for proliferation and apoptosis of rat vascular smooth muscle cells

摘要

摘要: 目的:研究老年大鼠血管平滑肌细胞（VSMCs）增殖和凋亡与p38信号转导通路的关系,明确以p38为靶向的信号转导在VSMCs中的分子调控机制。方法：将p38特异性抑制剂SB203580(25 μmol/L)作用于大鼠VSMCs，运用MTT比色法检测细胞增殖状态，流式细胞术检测SB203580对细胞凋亡的影响，Western blot法检测药物作用前后p38通路相关蛋白p38α、MKK3、GADD153和c-myc的表达及相关蛋白磷酸化活性。结果： SB203580可以时间、剂量依赖的方式抑制VSMCs增殖促进其凋亡。加入SB203580的VSMCs中p-p38α、GADD153和c-myc表达的水平，随作用时间的延长而下降（P<0.01）。结论：阻断p38信号转导通路可能通过下调其下游靶基因GADD153和C-myc的表达，抑制血管平滑肌细胞增殖，促进其凋亡。

Abstract: AIM:To investigate the relationship between p38 signal transduction pathway and the proliferation and apoptosis of vascular smooth muscle cells (VSMCs) in rats of old age and to establish a mechanism of p38-targeted treatment for VSMCs. METHODS: Rat VSMCs were treated with SB203580 (a selective p38 inhibitor). MTT assay and flow cytometry were used to measure proliferation and apoptosis. Expressions of p-p38, MKK3, GADD153 and C-myc proteins were measured by Western blot. RESULTS: SB203580 inhibited cell proliferation, induced apoptosis in a dose- and time-dependent manner and resulted in a significant downregulation of p-p38, GADD153 and C-myc (P<0.01). CONCLUSION: Our results show that blocked p38 signaling pathway induces apoptosis and inhibits proliferation of VSMC through decreasing the GADD153 and C-myc expression of p38 downstream target genes.

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