大鼠血管平滑肌细胞中以COX-2/JAK2/STAT3为靶向的信号转导分子调控机制的研究  

STAT3 signaling pathway mediates cyclooxygenase-2 selective inhibitory-induced apoptosis and inhibited proliferationIn of vascular smooth muscle cells

作　　者：唐梅[1] 张钲[1] 伏静媛 宁金民 王银娣 

机构地区：[1]兰州大学第一附属医院心内科,兰州730000 [2]兰州市第一人民医院心内科

出　　处：《临床心血管病杂志》2006年第7期428-431,共4页Journal of Clinical Cardiology

摘　　要：目的:研究转录信号转导子和激活子3(STAT3)信号转导通路与选择性环氧化酶2(COX-2)抑制剂调控血管平滑肌细胞(VSMC)增殖凋亡的关系,明确COX-2抑制剂作用的细胞内信号转导机制。方法:将选择性COX-2抑制剂NS-398,作用于鼠VSMCs,运用MTT法检测细胞增殖状态;流式细胞仪观察NS-398对细胞凋亡的影响,进一步用RT-PCR检测药物作用前后VSMCs中COX-2mRNA表达;Westernblot检测药物作用前后STAT3通路相关蛋白JAK2、STAT3、CyclinD1、Bcl-2的表达及磷酸化活性。结果:鼠VSMCs中COX-2mRNA呈高表达,NS-398呈时间、剂量依赖性方式抑制VSMCs细胞增殖,促进其凋亡。加入NS-398的VSMCs中COX-2mRNA表达水平显著下降(P<0·01)。同时P-JAK2、P-STAT3、CyclinD1、Bcl-2表达水平随作用时间延长而下降(P<0·01)。结论:选择性COX-2抑制剂NS-398对VSMCs作用与COX-2mRNA水平相关,癌基因Stat3信号转导通路调控了NS-398对VSMCs作用的细胞内信号转导机制,最终通过其下游靶基因CyclinD1、Bcl-2影响VSMCs的增殖与凋亡。Objective： To investigate the relationship between STAT3 signal transduction pathway and the mechanism of selective cyclooxygenase-2 inhibitor -NS-398 action against vascular smooth muscle cells（VSMCs）. Revealing the potential mechanism of NS-398 effect on VSMCs. Method..VSMCs of rat were treated with NS-398 （a selective COX-2 inhibitor）. MTT assay and flow cytometry were used to measure the proliferation and apoptosis. RT-PCR was performed on detecting the levels of COX-2 mRNA expression from VSMCs. The expression of STAT3, p-STAT3, JAK2, P-JAK2, Cyclin D1 and Bcl-2 proteins was measured by Western blot. Result.. High expression of COX-2 mRNA was detected VSMC and there was obvious decline of COX-2 mRNA after NS-398 treating（ P 〈0.01）. NS-398 inhibited the cells proliferation and induced apoptosis in a dose, time-dependent manner and resulted in significant downregulation of STAT3, p-STAT3, JAK2, P-JAK2, Cyclin D1, Bcl-2 （ P〈 0.01）. Conclusion.. Selective COX-2 inhibitor NS-398 may inhibit the proliferation and induce apoptosis of VSMCs through decreasing expression of COX-2 mRNA. STAT3 Signaling pathway mediates COX-2-selective inhibitor- induced apoptosis and proliferative inhibition in VSMCs,which may be a new target of selective COX-2 inhibitor effect on VSMCs.

关 键 词：血管平滑肌细胞 环氧化酶2抑制剂 转录信号转导子和激活子3 细胞凋亡 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]