阿托伐他汀钙对野百合碱介导肺动脉平滑肌细胞增殖与凋亡的影响  

Effect of Atorvastatin Calcium on the proliferation and apoptosis of monocrotaline-induced pulmonary artery smooth muscle cells

作　　者：黄军霞 李颖 范玉华[3] 涂应锋[4] HUANG Junxia LI Ying FAN Yuhua TU Yingfeng(The Third Department of Internal Medicine, Kaihua People＇s Hospital of Quzhou City, Zhejiang Province, Kaihua 324300, China the Second Department of Internal Medicine, Kaihua People＇s Hospital of Quzhou City, Zhejiang Province, Kaihua 324300, China College of Pharmacy, Harbin Medical University, Heilongjiang Province, Daqing 163000, China Department of Cardiology, the Fourth Hospital Affiliated to Harbin Medical University, Heilongjiang Province, Daqing 150001, China)

机构地区：[1]浙江省衢州市开化县人民医院内三科,浙江开化324300 [2]浙江省衢州市开化县人民医院内二科,浙江开化324300 [3]哈尔滨医科大学药学院,黑龙江大庆163000 [4]哈尔滨医科大学附属第四医院心内科,黑龙江哈尔滨150001

出　　处：《中国医药导报》2016年第34期8-12,F0004,共6页China Medical Herald

基　　金：国家自然科学基金青年科学基金项目(81401457);中国博士后科学基金面上项目(2014M561376);黑龙江省卫生计生委面上项目(2014-385);黑龙江省自然科学基金留学基金项目(LC2015038);黑龙江省博士后资助项目(LBH-Z14143)

摘　　要：目的探讨阿托伐他汀钙(ATV)对野百合碱诱导的肺动脉平滑肌细胞(PASMCs)增殖与凋亡作用及其分子机制。方法将PASMCs随机分为对照组、野百合碱组、野百合碱+ATV组以及野百合碱+ATV+SC79组。应用MTT法检测PASMCs细胞的生长情况,荧光TUNEL法分析PASMCs细胞凋亡情况,并用免疫印迹法检测PASMCs细胞中PI3K、AKT、p-AKT、Bcl-2以及Bax表达的变化。结果与对照组比较,野百合碱组PASMCs细胞增殖明显增强(P<0.01),ATV能明显抑制MCT诱导的PASMCs细胞增殖(P<0.01),且ATV可明显降低PI3K/AKT通路蛋白及Bcl-2蛋白的表达,而升高Bax蛋白的表达,诱导PASMCs细胞凋亡(P<0.01)。此外,AKT特异性激动剂SC79能逆转ATV的作用。结论 ATV通过作用于PI3K/AKT信号通路调控PASMCs细胞增殖,诱导细胞凋亡,为肺动脉高压治疗提供新的治疗策略。Objective To investigate the effects and molecular mechanism of Atorvastatin Calcium （ATV） on the prolif eration and apoptosis of pulmonary artery, smooth muscle cells （PASMCs） induced by monocrotaline. Methods The PASMCs were randomly assigned into four groups： control group, monoerotaline group, monocrotaline＋ATV group and monocrotaline＋ATV ＋SC79 group. The MTT assay was used to assess the proliferation of PASMCs cells. And the PASMCs apoptosis was analyzed by TUNE1 apoptosis assay kit. Furthermore, the expression of PI3K, AKT, p-AKT, Bcl-2 and Bax was determined by the Western blot assay. Results Compared with control group, the proliferation of PASMCs was obviously increased in monocrotaline group （P 〈 0.01）, while the ATV could inhibit the effect of monocro- taline in PASMCs （P 〈 0.01）, in addition, the expression of PI3K/AKT signal proteins and Bcl-2 protein in monocro- taline＋ATV treated PASMCs cells were decreased significantly, while the expression of Bax was increased significantly,and ATV could induce apoptosis in PASMCs （P 〈 0.01）. However, the SC79, a unique specific AKT activator, could reverse the effect of ATV on PASMCs. Conclusion ATC has protective effects on the proliferation and apop- tosis of pulmonary artery smooth muscle cells via PI3K/ AKT signal pathway, which might be a novel strategy for treating pulmonary artery hypertension.

关 键 词：肺动脉高压 阿托伐他汀钙 野百合碱 PI3K/AKT 凋亡 

分 类 号：R543.204[医药卫生—心血管疾病]