益气活血药对心梗大鼠心肌细胞肥大和HDAC4-MEF2C的影响  

Effects of Yiqi Huoxue pills on HDAC4-MEF2C and cardiomyocyte hypertrophy in rats with myocardial infarction

作　　者：谭晓波[1] 郭书文[1] 黄小楼[1] 蔡倩[1] 李芳赫 王惠[1] 吴佳妮[1] 林王欧 张宇沁 张彬月 TAN Xiaobo;GUO Shuwen;HUANG Xiaolou(Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,硕士研究生100029

出　　处：《环球中医药》2018年第6期812-818,共7页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81473552)

摘　　要：目的观察益气活血药对心梗大鼠心肌细胞肥大和组蛋白去乙酰化酶4(histone deacetylases4,HDAC4)-肌细胞增强因子(myocyte enhancer facter 2C,MEF2C)的影响,探讨益气活血药影响心肌细胞肥大的机制。方法结扎左冠状动脉前降支构建心肌梗死大鼠模型,并随机分为模型组、培哚普利组、益气活血组,另设假手术组只穿线不结扎,每组大鼠15只。术后两天灌胃给药,以7、28天为观测点。小动物超声检测各组大鼠心脏结构和功能的变化,HE染色观察心肌病理形态改变,用Western blot法检测大鼠心肌梗死边缘区HDAC4及其磷酸化蛋白p-HDAC4的表达,用RT-PCR法检测MEF2C mRNA的表达。结果模型组大鼠与假手术组相比,心脏左室射血分数(left ventricular ejection fraction,LVEF)、左室短轴率(left ventricular fractional shortening,LVFS)显著降低(P<0.01),左室收缩末期内径(left ventricular internal dimension systole,LVIDs)、左室舒张末期内径(left ventricular end diastolic diameter,LVIDd)显著升高(P<0.01);与模型组相比,各给药组LVEF、LVFS均显著升高(P<0.05,P<0.01);术后28天,益气活血组LVIDs、LVIDd显著低于模型组(P<0.01)。与假手术组比较,模型组和用药组的心肌细胞的横截面面积明显增大(P<0.01);与模型组比较,用药组的心肌细胞的横截面积降低(P<0.01,P<0.05)。模型组大鼠HDAC4表达显著高于假手术组(P<0.01),用药组与模型组相比有所降低但差异无统计学意义。模型组大鼠p-HDAC4蛋白表达显著高于假手术组(P<0.01),7天时,用药组大鼠表达量显著低于模型组(P<0.01);28天时,益气活血组与模型组相比有所降低(P<0.05)。模型组大鼠MEF2C mRNA均高于假手术组(P<0.01),用药组与模型组相比MEF2C mRNA表达降低(P<0.01,P<0.05)。结论益气活血药可能通过抑制HDAC4磷酸化影响HDAC4-MEF2C通路异常病理信号传导减轻心梗大鼠心肌细胞肥大水平。Objective To observe the effects of Yiqi Huoxue pills on myocardial hypertrophy and HDAC4-MEF2C in rats with 1wocardial infaretion ction, and to explore the mechanism of Yiqi Huoxue pills in in- fluencing cardiolwocyte hypertrophy. Methods The left anterior descending coronary artery was ligated to construct a rat model of 1wocardial intarction, and randomly divided into model group, perindopril group, Yiqi Huoxue group. The sham operation group was only ligated without threading, 15 rats in each group. 2 days after the operation, intragastric administration was perlbnned at 7,28 days as the observation point. The changes of heart structure and tunction were observed by small animal ultrasound. HE staining was used to observe the pathological changes of 1wocardium. Western blot was used to detect the expression of HDAC4 and its phosphon protion protein p-HDAC4 in rat myocardial intarct margin. RT-PCR was used to detect the expression of MEF2C mRNA. Results Compared with the sham-operated group, the left ventricular ejection ti＇action （LVEF） and left ventficular short axis rate （LVFS） of the model group rats were signifi- cantly decreased （P〈0.01） ,while left ventricular end-systolic diameter （LVIDs）, left ventricular diastolic tunction LVIDd was significantly increased （P〈 0.01 ）. Compared with the model group, the LVEF and LVFS were significantly increased in all groups （P〈0.05,P〈0.01） ; 28 days after operation,the Qi-stimu- lating blood group LVIDs and LVIDd were significantly lower than those in the model group （P〈0.01）. Compared with the sham-operated group,the cross-sectional area of cardiolwocytes in the model group and the drug group increased significantly （P〈0.01）. Compared with the model group,the cross-sectional area of the myocardial cells in the drug group decreased （P〈0.01 ,P〈0.05）. The expression of HDAC4 in the model group was significantly higher than that in the sham group （P〈0.01）. The dose of HDAC4 in the model group was lower than th

关 键 词：益气活血药 组蛋白去乙酰化酶4 肌细胞增强因子2C 心肌细胞肥大 

分 类 号：R285.5[医药卫生—中药学]