肝X受体激动剂GW3965对大鼠糖尿病心肌病的影响  

The Effect of Liver X Receptors Agonist GW3965 on Rats with Diabetic Cardiomyopathy

作　　者：成永霞[1] 王翀[1] 徐彪[2] 王莹[1] 颜彬[1] 

机构地区：[1]牡丹江医学院,黑龙江牡丹江157011 [2]牡丹江医学院附属红旗医院,黑龙江牡丹江157011

出　　处：《贵州医科大学学报》2017年第2期155-158,164,共5页Journal of Guizhou Medical University

基　　金：国家青年科学基金项目(81500629)

摘　　要：目的:研究肝X受体(LXRs)激动剂GW3965对链脲佐菌素(STZ)诱导的糖尿病心肌病大鼠心室功能、血脂代谢和心肌细胞凋亡的影响。方法:健康雄性清洁级SD大鼠,均分为对照组、模型组和GW3965组,模型组和GW3965组大鼠腹腔注射STZ建立糖尿病模型,对照组给予等量生理盐水处理;8周后GW3965组皮下注射GW3965(50 mg/kg),每周1次,连续4周,模型组及对照组大鼠皮下注射等体积无菌生理盐水;末次给药后监测各组大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)及左室内压最大变化速率(±dp/dtmax),测定大鼠血清血脂总胆固醇(TC)、甘油三酯(TG)及游离脂肪酸(NEFA),观察各组大鼠病理学及心肌细胞凋亡情况。结果:与对照组比较,模型组大鼠LVEDP、血清TC、TG、NEFA的含量明显升高,而LVSP、±dp/dtmax显著降低(P<0.05或P<0.01);与模型组比较,GW396组大鼠的LVSP、±dp/dtmax显著升高,LVEDP、血清TC、TG、NEFA显著降低(P<0.05或P<0.01);对照组大鼠心肌纹理清晰、致密,心肌细胞形态正常;模型组大鼠心肌细胞肥大,心肌结构紊乱,心肌纤维损伤、断裂明显;与模型组比较,GW396组大鼠心肌细胞病变、坏死程度显著减轻,肌纤维断裂情况明显好转;对照组大鼠心肌细胞核呈蓝色,未见凋亡;模型组大鼠心肌组织中出现棕黄色颗粒,心肌细胞发生大量凋亡;与模型组比较,GW396组大鼠心肌组织中棕黄色颗粒显著减少,心肌细胞发生凋亡情况减少。结论:LXRs激动剂GW3965对糖尿病心肌病大鼠具有保护作用,可以改善心功能,抑制心肌细胞凋亡。Objective：To investigate the effect of liver x receptors（LXRs） agonist GW3965 on ventricular function,lipid metabolism and myocardial apoptosis in rats with diabetic cardiomyopathy induced by streptozotocin（STZ）.Methods：Healthy male SD rats（200 ~ 250 g） were randomly divided into three groups：control group,model group and GW3965 group.The rats in model group and GW3965 group were injected with STZ intraperitoneally to establish diabetic model; control group was treated with equal volume of saline.After eight weeks,GW3965 group was injected with GW3965（50 mg/kg） subcutaneously,once a week for four weeks; model group and control group was injected with equal volume of sterilized saline; after the last administration,LVSP,LVEDP and ± dp/dtmaxwere monitored; testing TC,TG and NEFA of rats and observing pathology and myocardial apoptosis of rats.Results：Comparing with control group,content of LVEDP,TC,TG and NEFA obviously increased,while LVSP and ± dp/dtmax obviously decreased（P〈0.05 or P〈0.01）; comparing with model group,LVSP and ± dp/dtmax of GW396 Group rats obviously increased,content of LVEDP,TC,TG and NEFA obviously decreased（P〈0.05 or P〈0.01）; myocardial texture of control group rats was clear and tight,cardiomyocytes morphology was normal; while in model group rats,myocardial texture was fat,myocardial structure was disorder,cardiac muscle fibers was damaged with clear fracture; comparing with model group,cardiomyocytes of GW396 group rats had lesion,necrosis degree was alleviated,muscle fiber fracture was obviously improved; myocardial nuclear of control group rats were blue with no apoptosis; cardiac muscular tissue of model rats discovered brown and yellow particles,large scale apoptosis of cardiomyocytes were found; comparing with model group,cardiac muscular tissue of GW396 group found obvious decreased brown and yellow particles,cardiomyocytes apoptosis decreased.Conclusion：GW3965,the LXRs agonist,has protective effect on rats with diabetic cardiomyopathy via

关 键 词：糖尿病心肌病 大鼠 Sprague-Dawley 模型 动物 心功能 血脂代谢 细胞凋亡 

分 类 号：R587.23[医药卫生—内分泌] R542.2[医药卫生—内科学]