Rev-erb激动剂GSK4112对心肌梗死大鼠心肌损伤和心脏重塑的影响  

Effects of Rev-erb agonist GSK4112 on myocardial injury and cardiac remodeling in rats with myocardial infarction

作　　者：周中淑 傅春江 邹雪 唐黎 ZHOU Zhongshu;FU Chunjiang;ZOU Xue;TANG Li(Internal Medicine-Cardiovascular Department,Third Affiliated Hospital of Military Medical University,Chongqing 400042,China)

机构地区：[1]陆军军医大学第三附属医院心血管内科,重庆400042

出　　处：《山西医科大学学报》2019年第2期125-130,共6页Journal of Shanxi Medical University

摘　　要：目的观察Rev-erb激动剂GSK4112对心肌梗死大鼠的心肌损伤和心脏重塑的影响,并探讨作用机制。方法 10周龄雄性Wistar大鼠48只随机分为四组:假手术对照组(n=12)、假手术给药组(n=12)、实验对照组(n=12)和实验给药组(n=12)。实验组给药组建立心肌梗死模型;皮下注射100μg/kg Rev-erb激动剂GSK4112。实验对照组建立心肌梗死模型;皮下注射100μg/kg生理盐水。假手术给药组仅切开皮肤;皮下注射100μg/kg Rev-erb激动剂GSK4112。假手术对照组仅切开皮肤;皮下注射100μg/kg生理盐水。造模后2 h取标本,检测各大鼠的心肌梗死面积、梗死壁厚度、心肌细胞凋亡、梗死边缘区血管新生,TUNEL染色阳性率表征心肌细胞凋亡,测定心脏重塑指标(D/L、LVEDd、IVST、LVPWT、LVM和LVMI),采用ELISA法分别检测血清IL-1β、IL-6和TNF-α水平。结果实验对照组心肌梗死面积为(51. 32±2. 40)%,实验给药组心肌梗死面积为(43. 96±1. 75)%(P <0. 05)。实验对照组心肌梗死壁厚度为(0. 38±0. 01) mm,实验给药组心肌梗死壁厚度为(0. 54±0. 02) mm(P <0. 05)。实验对照组心肌细胞凋亡率高达(6. 02±0. 57)%,实验给药组细胞凋亡率降为(3. 79±0. 21)%(P <0. 05)。实验对照组心肌梗死边缘区血管密度为31.65±2.38,实验给药组心肌梗死边缘区血管密度为48. 96±3. 55(P <0. 05)。实验给药组的D/L、LVEDd、LVPWT、LVM和LVMI低于实验对照组(P <0. 05)。实验给药组的D/L、LVEDd、和LVM均高于假手术对照组和假手术给药组(P <0. 05)。实验对照组炎症因子IL-1β、IL-6和TNF-α水平高于假手术对照组和假手术给药组(P <0. 05)。实验对照组炎症因子IL-1β、IL-6和TNF-α水平低于实验对照组(P <0. 05),但高于假手术对照组和假手术给药组(P <0. 05)。结论 Rev-erb激动剂GSK4112能够降低心肌梗死后大鼠机体内炎症因子IL-1β、IL-6和TNF-α水平,从而改善心肌梗死后心肌缺血损伤和阻止心脏重塑。Objective To investigate the effect of GSK4112,a Rev-erb agonist,on myocardial injury and cardiac remodeling in rats with myocardial infarction,and to explore its mechanism.Methods Forty-eight 10-week-old male Wistar rats were randomly divided into four groups:sham-operated control group(n=12),sham-operated administration group(n=12),experimental control group(n=12)and experimental administration group(n=12).The model of myocardial infarction was established in experimental administration group,and then the model rats were hypodermically injected with 100 g/kg GSK4112.The model of myocardial infarction was established in experimental control group,and the rats were hypodermically injected with 100μg/kg normal saline.Only the skin of rats was only cut in sham administration group,and the rats were hypodermically injected with 100 g/kg GSK4112.Only the skin of rats was cut in sham control group,and the rats were hypodermically injected with 100μg/kg normal saline.The specimens were taken 2 h after modeling.Myocardial infarct size,infarct wall thickness,apoptosis of myocardial cells,angiogenesis of infarct margin were measured.Myocardial apoptosis was characterized by positive rate of TUNEL staining.Cardiac remodeling indexes(D/L,LVEDd,IVST,LVPWT,LVM and LVMI)were measured.Serum levels of IL-1β,IL-6 and TNF-αwere detected by ELISA.Results The myocardial infarction area was(51.32±2.40)%in experimental control group and(43.96±1.75)%in experimental administration group(P<0.05).The wall thickness of myocardial infarction was(0.38±0.01)mm in experimental control group and(0.54±0.02)mm in experimental administration group(P<0.05).The apoptosis rate of myocardial cells was up to(6.02±0.57)%in experimental control group,and down to(3.79±0.21)%in experimental administration group(P<0.05).The vascular density in the peripheral area of myocardial infarction was 31.65±2.38 in experimental control group,and 48.96±3.55 in experimental administration group(P<0.05).D/L,LVEDd,LVPWT,LVM and LVMI were lower in experimental

关 键 词：Rev-erb激动剂 心肌梗死 心肌缺血性损伤 心脏重塑 大鼠 

分 类 号：R542.22[医药卫生—心血管疾病]