间尼索地平通过Rho/ROCK通路抑制5-羟色胺诱导的大鼠肺动脉平滑肌细胞增殖  

m-Nisodipine inhibited 5-HT-induced proliferation of rat PASMCs through Rho/ROCK signal pathway

作　　者：刘焕龙[1] 于丁[1] 朱忠宁 苏素文 陈雪彦 张永健 

机构地区：[1]河北医科大学第二医院,河北石家庄050000 [2]基础医学院,河北石家庄050017

出　　处：《药学学报》2015年第7期824-829,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81273600);河北省自然科学基金资助项目(H2013206147,C2011206145)

摘　　要：探讨Rho/ROCK通路在5-羟色胺（5-HT）诱导的大鼠肺动脉平滑肌细胞（PASMCs）增殖中的作用以及间尼索地平（m-Nis）对此的影响。组织贴块法原代培养大鼠PASMCs;噻唑蓝（MTT）比色法观察1μmol·L-15-HT作用不同时间对大鼠PASMCs增殖的影响以及m-Nis的干预作用;Western blot及RT-PCR等方法检测5-HT作用下大鼠PASMCs增殖中Rho A、ROCK1 m RNA和p-MYPT1蛋白表达的变化以及m-Nis对此的影响,深入探讨其作用机制。结果显示：1μmol·L-1 5-HT作用12-72 h可明显诱导大鼠PASMCs增殖（P〈0.05或P〈0.01）;m-Nis（1×10-5、1×10-6、1×10-7和1×10-8 mol·L-1）均可明显抑制5-HT诱导的大鼠PASMCs增殖,并呈现一定的浓度依赖性（P〈0.05或P〈0.01）;另外,不同浓度m-Nis还明显抑制了5-HT诱导的Rho A和ROCK1 m RNA的表达以及ROCK的活化（P〈0.05或P〈0.01）。结果表明Rho/ROCK通路在5-HT诱导的大鼠PASMCs增殖中起重要作用,m-Nis明显抑制了5-HT诱导的大鼠PASMCs增殖,该作用可能与其抑制Rho/ROCK通路有关。This paper is to report the exploration of the activation of Rho/ROCK signal pathway in 5-HT- induced proliferation of rat pulmonary artery smooth muscle cells（PASMCs） and the inhibitory effect of m-Nis on this pathway. PASMCs were cultured with the explant technique. MTT assay was used to explore the proliferation of PASMCs after 5-HT treated for different time and the intervening effect of m-Nis. RT-PCR and Western blot were used respectively to explore the m RNA expression of Rho A, ROCK1 and the protein expression of p-MYPT1 in 5-HT-treated PASMCs and intervening effect of m-Nis. The results of MTT assay suggested that 5-HT（1 μmol·L-1） treatment for 12-72 h significantly induced the proliferation of rat PASMCs（P〈 0.05 or P〈 0.01）, which were inhibited by m-Nis（1×10-5, 1×10-6, 1×10-7, 1×10-8 mol·L-1） in dose-dependent manners（P〈 0.05 or P〈 0.01）. Similarly, the m RNA expression of Rho A, ROCK1 and the protein expression of p-MYPT1 were also inhibited by m-Nis in different degrees（P〈 0.05 or P〈 0.01）. Thus, the results of this study suggested that Rho/ROCK pathway played an important role in 5-HT-induced proliferation of rat PASMCs, m-Nis inhibited 5-HT-induced proliferation obviously, which may be related to the blockage of Rho/ROCK signal pathway.

关 键 词：间尼索地平 5-羟色胺 肺动脉平滑肌细胞 增殖 RHO激酶 

分 类 号：R963[医药卫生—微生物与生化药学]