瑞舒伐他汀对风湿性心脏病伴心房颤动患者心房成纤维细胞体外增殖与凋亡的影响  

Effect of rosuvastatin on proliferation and apoptosis of atrial fibroblasts in patients with rheumatic heart disease and atrial fibrillation in vitro

作　　者：段长恩 秦卫玲[2] 智明星 郭晓亮[3] 周朝元[1] 韩培立[1] DUAN Chang′en;QIN Weiling;ZHI Mingxing;GUO Xiaoliang;ZHOU Chaoyuan;HAN Peili(Department of Cardiovascular Surgery,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;Department of Hematopathy,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Department of Cardiovascular Medicine,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China)

机构地区：[1]新乡医学院第一附属医院心血管外科,河南卫辉453100 [2]新乡医学院第三附属医院血液内科,河南新乡453003 [3]新乡医学院第一附属医院心血管内科,河南卫辉453100

出　　处：《新乡医学院学报》2020年第6期517-521,共5页Journal of Xinxiang Medical University

基　　金：新乡医学院第一附属医院青年基金项目(编号:QN-2017-B005)。

摘　　要：目的探讨瑞舒伐他汀对风湿性心脏病伴心房颤动(AF)患者心房成纤维细胞体外增殖与凋亡的影响。方法选择2018年1~12月在新乡医学院第一附属医院心血管外科确诊为风湿性心脏病伴永久性AF患者50例为研究对象,获取患者左心耳组织并应用Massion染色观察其纤维化程度;分离左心耳组织中成纤维细胞,将细胞分为对照组、10-5mol·L^-1瑞舒伐他汀(ROS)组、10-6mol·L^-1ROS组、10-7mol·L^-1ROS组、10-5mol·L^-1ROS+10-5mol·L^-1焦磷酸法尼酯(FPP)组、10-6mol·L^-1ROS+10-5mol·L^-1FPP组、10-7mol·L^-1ROS+10-5mol·L^-1FPP组,分别加入含对应上述终浓度药物的达尔伯克改良伊格尔培养基(DMEM)100μL,共培养72 h,对照组细胞加入等量含体积分数10%胎牛血清的DMEM。采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法测各组成纤维细胞的增殖情况,Edu法测各组成纤维细胞DNA合成率,实时荧光定量聚合酶链反应法检测各组成纤维细胞中凋亡相关基因的表达。结果风湿性心脏病伴AF颤患者左心耳组织出现明显的成纤维细胞增生并伴有部分心肌细胞的凋亡和溶解,胶原容积分数为(10.25±1.10)%。各干预组细胞的增殖能力均低于对照组(P<0.05),10^-7mol·L^-1ROS+10^-5mol·L^-1FPP组、10^-6mol·L^-1ROS+10-5mol·L^-1FPP组、10^-5mol·L^-1ROS+10^-5mol·L^-1FPP组细胞增殖能力均高于对应浓度ROS组(P<0.05)。各干预组细胞DNA合成率均低于对照组(P<0.05),10^-7mol·L^-1ROS+10^-5mol·L^-1FPP组、10^-6mol·L^-1ROS+10^-5mol·L^-1FPP组、10^-5mol·L^-1ROS+10^-5mol·L^-1FPP组细胞DNA合成率均高于对应浓度ROS组(P<0.05)。各干预组细胞抗凋亡基因Bcl-2和凋亡抑制蛋白-1(IAP-1)相对表达量均低于对照组(P<0.05),促凋亡基因Bax和Smac相对表达量均高于对照组(P<0.05);10-7mol·L^-1ROS+10^-5mol·L^-1FPP组、10^-6mol·L^-1ROS+10^-5mol·L^-1FPP组、10^-5mol·L^-1ROS+10^-5mol·L^-1FPP组细胞抗凋亡基因Bcl-2和IAP-1的相对表达量均高�Objective To study the effect of rosuvastatin(ROS)on the proliferation and apoptosis of atrial fibroblasts in patients with rheumatic heart disease and atrial fibrillation(AF)in vitro.Methods Fifty patients with rheumatic heart disease and permanent AF in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Xinxiang Medical University from January to December 2018 were selected as the study objects.The left auricular tissue of patients was obtained and the degree of fibrosis was observed by Massion staining.Then the fibroblasts isolated from the left auricular tissue and then were divided into control group,10^-5 mol·L^-1 ROS,10^-6 mol·L^-1 ROS group,10^-7 mol·L^-1 ROS group,10^-5 mol·L^-1 ROS+10^-5 mol·L^-1 farnesyl pyrophosphate(FPP)group,10^-6 mol·L^-1 ROS+10^-5 mol·L^-1 FPP group,10^-7 mol·L^-1 ROS+10^-5 mol·L^-1 FPP group.The cells in above intervention groups were given 100μL Dulbecco′s modified Eagle medium(DMEM)containing the corresponding final concentration of the above drugs and co-cultured for 72 hours;the cells in control group were given the same volume of DMEM medium containing 10%fetal bovine serum.The proliferation and DNA synthesis of the fibroblasts were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Edu method respectively.The expression of apoptosis related genes were detected by real-time fluorescence quantitative polymerase chain reaction.Results The left auricular tissue of the patients with rheumatic heart disease and permanent AF showed the obvious proliferation of fibroblasts and some cardiac myocytes appeared apoptosis and dissolution.The collagen volume fraction was(10.25±1.10)%.The proliferation ability of fibroblasts in all intervention groups was lower than that in the control group(P<0.05),the proliferation ability of fibroblasts in 10^-7 mol·L^-1 ROS+10^-5 mol·L^-1 FPP group,10^-6 mol·L^-1 ROS+10^-5 mol·L^-1 FPP group,10^-5 mol·L^-1 ROS+10^-5 mol·L^-1 FPP group was higher than that in the corresponding conce

关 键 词：风湿性心脏病 心房颤动 瑞舒伐他汀 增殖 凋亡 

分 类 号：R541.2[医药卫生—心血管疾病]