Notch蛋白在心肌梗死后大鼠心肌中的表达及益气活血方干预的研究

Expression of Notch protein in myocardium of acute myocardial infarction rats and intervention of Yiqi Huoxue Formula

目的通过构建急性心肌梗死模型,探讨Notch信号蛋白在心肌梗死后大鼠心肌中的表达及益气活血方对其干预作用。方法清洁级SD大鼠64只,随机分为假手术组、模型组、益气活血组、培哚普利组,以第7天、第28天2个时间窗进行观察,左冠状动脉前降支结扎构建急性心肌梗死模型,术后第2天开始灌胃给药。采用小动物超声系统检测各组大鼠心脏左室射血分数(LVEF)、左室短轴率(LVFS),HE染色观察心肌病理形态改变,蛋白印迹法测定Notch1、Notch3、Notch4蛋白相对表达水平。结果与假手术组比较:第7天、第28天模型组LVEF、LVFS显著减少(P<0.01),梗死边缘区心肌细胞数量减少,可见炎性细胞浸润,Notch1蛋白表达显著增加(P<0.01),Notch3蛋白表达仅在第7天增加(P<0.01)。与模型组比较:第7天益气活血组LVEF、LVFS显著减少(P<0.05),Notch1、Notch3蛋白表达显著减少(P<0.05),第28天益气活血组LVEF显著增加(P<0.05),Notch1蛋白表达显著减少(P<0.01)。结论益气活血方能够改善心肌梗死大鼠心脏功能,并且长期应用疗效更佳,其生物学机制可能与心肌梗死损伤修复相关蛋白Notch1、Notch3有关。

Objective By establishing the acute myocardial infarction（AMI）model,toinvestigatethe expression of Notch signal protein in the myocardium of AMI model rats and the repair ment mechanism of Yiqi Huoxue Formula（supplementing qi and activating blood form ula）oncardiacinjury.Methods Al-together 64 SD rats,SPF grade,were randomly divided into sham group,model group,Yiqi Huoxue For-mula （TCM）group,perindopril group.The AMI model was induced by ligation of left coronary artery. Since the next day,the rats in TCM group and perindopril group were intragastrically （i.g.）adminis-tered corresponding drugs,with rats in sham group and model group administered distilled water.On Day 7 and Day 28,left ventricular ejection fraction （LVEF）and left ventricular fractional shortening （LVFS） were measured using visual sonic system designed exclusively for laboratory animals,pathological mor-phology was examined using HE staining,and the protein expressions of Notch 1 ,Notch 3 and Notch 4 weredetectedusing Westernblot.Results Comparedwithshamgroups,LVEF and LVFSinmodel he number of myocardial cells in the infarct border area decreased and inflammatory cells were observed.Notch 1 expression increased on both time points （P〈0.01）,Notch 3 expressed increasingly only on Day 7 （P〈0.05）.After interven-tion of TCM,LVEF,LVFS,Notch1 ,Notch3 decreased significantly compared with model group on Day 7 （P〈0.05 ）,LVEF increased significantly and Notch 1 expression decreased significantly on Day 28 （P〈0.01）.Conclusion Yiqi Huoxue Formula can improve cardiac function in rats with AMI,and lon-ger term application is more efficacy.Its biological mechanism maybe related to the injury related protein Notch 1 and Notch 3 .