阿托伐他汀对兔心肌梗死后miR-126表达和左心室重构的干预研究  

Study of atorvastatin on miR-126 expression and left ventricle remodeling in rabbits after acute myocardial infarction

作　　者：苏莉 谈红 郑德志 陈瑞敏 杨燕 韩淑芳 晋群 SU Li;TAN Hong;ZHENG De-zhi;CHEN Rui-min;YANG Yan;HAN Shu-fang;JIN Qun(The First Geronotology Department,The 960th Hospital of the Chinese People Liberation Army,Jinan 250031,China;Cardiovascular Department,The 960th Hospital of the Chinese People Liberation Army,Jinan 250031,China;Cardiovascular Surgery Department,The 960th Hospital of the Chinese People Liberation Army,Jinan 250031,China)

机构地区：[1]解放军第九六〇医院干部一科,山东省济南市250031 [2]解放军第九六〇医院心内科,山东省济南市250031 [3]解放军第九六〇医院心外科,山东省济南市250031

出　　处：《中国心血管病研究》2022年第11期1009-1013,共5页Chinese Journal of Cardiovascular Research

基　　金：解放军第九六〇医院院长基金面上项目(2013MS05)。

摘　　要：目的探讨不同剂量阿托伐他汀对急性心肌梗死(AMI)后兔心肌组织微小RNA-126(miR-126)表达及左室重构的影响。方法在解放军第960医院动物实验中心建立兔AMI模型,40只新西兰大白兔(体重3~4 kg),随机数字表法分为对照组(7只)、AMI组(11只)和低剂量阿托伐他汀组(11只)、高剂量阿托伐他汀组(11只)。4周时测定左心室射血分数(LVEF)、每搏输出量(SV)、左心室短轴缩短率(LVFS),取梗死区心肌组织,HE染色观察组织细胞形态,Masson染色观察心肌胶原含量,RT-PCR法检测心肌miR-126表达。结果与对照组比较,AMI组坏死心肌存在严重的心肌纤维化,胶原含量明显增加[(58.12±9.80)%比(4.51±1.42)%,P<0.01],心肌miR-126表达水平显著降低[(0.63±0.07)比(1.03±0.04),P<0.01],左心室收缩功能指标均显著降低(P<0.01):LVEF[(44.18±4.35)%比(59.86±3.58)%]、SV[(3.92±0.34)ml比(6.70±0.71)ml]、LVFS[(20.01±2.12)%比(29.76±1.53)%]。阿托伐他汀治疗后心肌纤维化程度明显减轻,胶原含量明显降低[(47.65±10.17)%,P<0.01],以高剂量组变化更为显著[(39.80±9.89)%,P<0.01]。低剂量阿托伐他汀组LVEF[(48.09±4.46)%]、SV[(5.26±0.59)ml]、LVFS[(23.25±2.13)%]有一定程度增加(P<0.01),高剂量他汀组升高更为显著。心肌组织miR-126表达水平在低剂量阿托伐他汀组和高剂量阿托伐他汀组均较AMI组明显升高[(1.87±0.07),(2.42±0.19),P<0.01]。结论阿托伐他汀可显著改善心肌梗死后左室重构,且作用呈剂量依赖性,其作用机制可能与促进梗死心肌组织miR-126的表达有关。Objective To explore the effects of different dose atorvastatin on micro RNA-126(miR-126)expression and left ventricle remodeling in rabbits after acute myocardial infarction(AMI).Methods Rabbit model of acute myocardial infarction was established in the Animal Experimental Center of the 960th Hospital of PLA.40 New Zealand rabbits were randomly divided into 4 groups:the control group(n=7),AMI group(n=11),low(n=11)and high dose atorvastatin group(n=11).Left ventricular ejection fraction(LVEF),stroke volume(SV)and left ventricular fractional shortening(LVFS)were measured at the end of 4th weeks.Then the infarcted heart tissues were collected,and the outlooks of cardiomyocytes were observed after HE stain;the collagen contents in infarcted area were monitored after Masson stain;the expressions of miR-126 were detected by RT-PCR method.Results Compared with the control group,many cardiomyocytes of infarcted area in the AMI group were replaced by collagen fiber and the collagen contents were also increased significantly(58.12±9.80%vs.4.51±1.42%,P<0.01).The expressions of miR-126 in cardiomyocytes were significantly higher in the AMI group than those in the control group(0.63±0.07 vs.1.03±0.04),and left ventricular systolic functions were significantly decreased(P<0.01):LVEF[(44.18±4.35)%vs.(59.86±3.59)%]、SV[(3.92±0.34)ml vs.(6.70±0.71)ml]、LVFS[(20.01±2.12)%vs.(29.76±1.53)%].After treated with atorvastatin,the degrees of fibrosis in cardiomyocytes were obviously improved and the collagen contents were significantly reduced[(47.65±10.17)%,P<0.01];and the changes were even more significant in the high dose atorvastatin group[(39.80±9.89)%,P<0.01].Low dose artorvastatin treatment significantly enhance systolic function(P<0.01):LVEF[(48.09±4.46)%]、SV[(5.26±0.59)ml]、LVFS[(23.25±2.13)%],and the changes in the high dose group were more obvious.The expressions of miR-126 in the cardiomyocytes,both in the low dose artovastatin group(1.87±0.07)and high dose artovastatin group(2.42±0.19)were significantl

关 键 词：急性心肌梗死 心室重构 阿托伐他汀 MIR-126 

分 类 号：Q95-33[生物学—动物学] R542.22[医药卫生—心血管疾病]