硝苯地平和氢氯噻嗪对机械牵拉力诱导的小鼠血管平滑肌细胞ERK1/2磷酸化和Ki67表达的影响  

Effects of Nifedipine and Hydrochlorothiazide on ERK1/2 Phosphorylation and Ki67 Activation of Mouse Vascular Smooth Muscle Cells Induced by Mechanical Stretch Stress

作　　者：汪泓[1] 王晶晶[1] 郭映纯 刘树迎[1] 平苏宁 刘科峰[1] 周玉环[1] 裴婷[1] 李朝红[1] 

机构地区：[1]中山大学中山医学院组织胚胎学教研室,广东省广州市510080 [2]中山大学中山医学院

出　　处：《中国动脉硬化杂志》2015年第4期347-351,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助(30871023;81070124);广东省自然科学基金资助(S2012010009199);高等学校博士学科点专项科研基金资助(20090171110049)

摘　　要：目的探讨钙离子阻滞剂硝苯地平和利尿剂氢氯噻嗪对机械牵拉力刺激诱导的血管平滑肌细胞(VSMC)ERK1/2磷酸化和Ki67表达的影响。方法体外培养静息状态下的VSMC,在分别给予硝苯地平和氢氯噻嗪预处理后给予机械牵拉力刺激。用免疫印迹法检测细胞内ERK1/2磷酸化水平;对细胞进行免疫荧光染色,检测Ki67表达水平。结果与阴性对照组相比,硝苯地平或氢氯噻嗪对静息培养的VSMC中ERK1/2磷酸化和Ki67的表达无影响;单纯机械力牵拉刺激,可引起静息培养的VSMC中ERK1/2磷酸化和Ki67的表达明显增加;硝苯地平可呈浓度依赖性抑制机械力牵拉引起的ERK1/2磷酸化和Ki67表达的增加;而氢氯噻嗪与硝苯地平作用相反,可进一步协同增加机械力牵拉引起的上述作用。结论硝苯地平和氢氯噻嗪对机械牵拉力引起的VSMC中ERK1/2磷酸化和Ki67表达增加的作用完全相反,前者可抑制机械牵拉力引起的VSMC中ERK1/2磷酸化和Ki67的表达增加,后者相反,呈协同增加。Aim To investigate the effects of calcium blocker nifedipine and diuretic hydrochlorothiazide on mechanical stretch stress mediated phosphorylation of ERK1 /2( p-ERK1 /2) and expression of Ki67 in vascular smooth muscle cells( VSMC). Methods Cultured quiescent VSMC were pretreated with nifedipine and hydrochlorothiazide respectively and subjected to treatment with mechanical stretch stress. Level of p-ERK1 /2 in the treated cells was detected by Western blot and meanwhile Ki67 expression was detected by immunofluorescent staining. Results Compared with the negative control group,nifedipine or hydrochlorothiazide had no effects on p-ERK1 /2 and Ki67 expression in quiescent VSMC,while mechanical stretch stress stimulation significantly increased levels of p-ERK1 /2 and Ki67 expression,which was inhibited by nifedipine in a concentration-dependent manner,and synergistically enhanced by hydrochlorothiazide.Conclusions Hydrochlorothiazide synergistically promotes increased p-ERK1 /2 and Ki67 expression in VSMC induced by mechanical stretch stress,which can be inhibited by nifedipine in a concentration-dependent manner. These results provide novel mechanisms for traditional antihypertensive drugs.

关 键 词：硝苯地平 氢氯噻嗪 机械牵拉力 ERK1/2 KI67 

分 类 号：R544.1[医药卫生—心血管疾病]