间尼索地平对5-羟色胺诱导大鼠肺动脉平滑肌细胞增殖和迁移的影响及其机制  

The effect of m-Nisoldipine on 5-HT-induced proliferation,migration of rat PASMCs and the mechanisms

作　　者：陈雪彦[1] 刘焕龙[2] 潘振华[1] 张永健[1] 

机构地区：[1]河北医科大学药理学教研室,河北石家庄050017 [2]河北医科大学第二医院药剂科,河北石家庄050000

出　　处：《中国药理学通报》2010年第2期226-230,共5页Chinese Pharmacological Bulletin

基　　金：河北省卫生厅医学科学研究重点课题指导计划(No20090306)

摘　　要：目的探讨间尼索地平(m-Nis)对5-羟色胺(5-HT)诱导的大鼠肺动脉平滑肌细胞(PASMCs)增殖和迁移的影响,并深入研究其作用机制。方法采用植块法培养大鼠PASMCs。实验分为6组:空白对照组、5-HT(1μmol·L-1)组,m-Nis(10-5、10-6、10-7、10-8mol.L-1)组。噻唑蓝(MTT)比色法、Transwell迁移小室法分别测定PASMCs的增殖和迁移,Western blot法检测大鼠PASMCs中增殖细胞核抗原(PCNA)的蛋白表达及细胞外信号调节激酶1和2(ERK1/2)的磷酸化水平,研究m-Nis对ERK1/2/MAPK信号通路的影响。结果不同浓度m-Nis明显抑制了5-HT诱导的大鼠PASMCs增殖(P<0.05或P<0.01)和迁移(P<0.01),并呈现一定的浓度依赖性;另外,Western blot结果显示m-Nis对5-HT诱导的大鼠PASMCs中PCNA的蛋白表达有不同程度的抑制作用(P<0.05或P<0.01),10-5,10-6,10-7mol.L-1m-Nis还明显抑制了5-HT诱导的大鼠PASMCs中ERK1/2磷酸化水平的升高,p-ERK1/2/ERK1/2比值均有不同程度地降低(P<0.05或P<0.01)。结论m-Nis对5-HT诱导的大鼠PASMCs增殖和迁移有明显的抑制作用,可能与其抑制PCNA蛋白表达及ERK1/2/MAPK信号通路有关。Abstract ：Aim To explore the effect of m-Nisoldipine （m-Nis） on 5-HT-induced proliferation, migration of rat PASMCs and to study the mechanisms. Methods PASMCs were cultured with the explant technique,and were divided into 6 groups, control group, 5-HT （ 1 μmol · L^-1 ） group and m-Nis（ 10 ^-5,10 ^-6,10 ^-7,10^-8 mol · L^-1）group. MTT assay was used to evaluate the proliferation of PASMCs, and transwell chambers were used to detect the migration of PASMCs. In addition, the expression of PCNA and the phosphorylation of ERK1/2 were evaluated by Western blot analysis. Resuits m-Nis inhibited the proliferation （P 〈 0. 05 or P 〈0. 01 ） and migration （P 〈0. 01 ） of rat PASMCs induced by 5-HT obviously. Similarly, Western blot analysis of PCNA indicated that the expression of PCNA was significantly higher in 5-HT group than that in control group（P 〈 0. 01 ）. Whereas, in four m-Nis treated groups, the level of PCNA was markedly decreased （P 〈0. 05 or P 〈 0. 01 ）. Meanwhile, m-Nis 10^-5, 10^-6 and 10^-7 mol · L^- 1 pretreatment also reduced 5-HT-induced phosphorylation of ERK1/2 obviously （P 〈 0. 05 or P 〈 0. 01 ）. Conclusion m-Nis inhibits 5-HT-indueed proliferation and migration of rat PASMCs obviously,which may be related to the inhibition of PCNA expression and the blockage of ERK1/2/MAPK signal pathway.

关 键 词：间尼索地平 5-羟色胺 肺动脉平滑肌细胞 增殖 迁移 细胞外信号调节激酶 

分 类 号：R-332[医药卫生] R322.121