氟伐他汀抗氧化改善心肌梗死大鼠心室重塑

被引:2
作者
赵志宏
单江
项美香
徐耕
傅国胜
鲍晓峰
机构
[1] 浙江大学医学院附属第二医院,浙江大学医学院附属第二医院,浙江大学医学院附属第二医院,浙江大学医学院附属第二医院,浙江大学医学院附属第二医院,浙江大学医学院附属第二医院浙江杭州,浙江杭州,浙江杭州,浙江杭州,浙江杭州,浙江杭州
关键词
氟伐他汀/药理学; 投药,口服; 心肌梗塞/血液; 心室; 疾病模型,动物;
D O I
暂无
中图分类号
R96 [药理学];
学科分类号
100602 ; 100706 ;
摘要
目的:探讨氟伐他汀长期应用对SD大鼠心肌梗死(AMI)心室重塑过程的影响及其机制。方法:结扎雄性大鼠左冠状动脉前降支,复制心肌梗死模型,将大鼠分为2组,AMI组(n=7)以蒸馏水灌胃,氟伐他汀组(n=8)以氟伐他汀20mg.k-g1.-d1灌胃;另设假手术2组,分别以蒸馏水和氟伐他汀灌胃。8周后心脏超声、血液动力学、心脏形态学分析;检测血浆总胆固醇(Tch)、一氧化氮(NO)、脂质过氧化物(LPO)、谷胱甘肽过氧化物酶(GPx)和心肌LPO水平;激光共聚焦显微镜检测超氧阴离子和NO的分布;RT-PCR、免疫组化检测诱导型一氧化氮合酶(NOS2)、p22phox的mRNA和蛋白水平表达。结果:与AMI组比较,氟伐他汀组左室舒张末压降低[(18.24±6.58vs10.74±4.71)mmHg,P<0.05]、右室相对重量减轻[(0.92±0.19vs0.71±0.13)g/kg,P<0.05]、左室后壁厚度减少[(3.04±0.28vs2.60±0.36)mm,P<0.05];AMI后射血分数无影响,但肺相对重量减轻[(5.79±2.92vs3.69±0.68)g/kg,P<0.05];血浆和心肌LPO水平降低[(8.64±0.59vs7.71±0.66)μmol/L,P<0.05;(3.12±0.38vs1.93±0.40)ng/μg.pro,P<0.01],NO的过度表达抑制和GPx水平增加[(436.87±47.22vs313.78±34.35)mg/dl,P<0.01;(66.13±8.31vs79.78±2.38)mg/dl,P<0.05]。氟伐他汀干预后增加NOS2、p22phoxmRNA和蛋白水平的表达均下降(P<0.01)。血浆总胆固醇水平减低,但无显著性差异[(59.40±14.15vs48.30±8.83)mg/dl,P>0.05]。结论:氟伐他汀参与了改善大鼠心肌梗死后心室重塑过程,其中可能包括抗氧化机制。
引用
收藏
页码:447 / 453+464 +464
页数:8
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