HDAC3在心肌缺血再灌注诱发糖尿病大鼠肾损伤中的作用  

Role of HDAC3 in renal injury induced by myocardial ischemia-reperfusion in diabetic rats

作　　者：明浩 邱珍[1] 夏中元[1] 雷少青[1] 赵博[1] Ming Hao;Qiu Zhen;Xia Zhongyuan;Lei Shaoqing;Zhao Bo(Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《中华麻醉学杂志》2019年第8期993-995,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81671891)。

摘　　要：目的评价组蛋白去乙酰化酶3(HDAC3)在心肌缺血再灌注诱发糖尿病大鼠肾损伤中的作用。方法SPF级健康成年雄性SD大鼠,体重210~220 g,采用腹腔注射1%链脲佐菌素60 mg/kg的方法制备大鼠糖尿病模型,取糖尿病模型制备成功的大鼠18只,采用随机数字表法分为3组(n=6):假手术组(S组)、心肌缺血再灌注组(I/R组)和HDAC3抑制剂组RGFP966(RG组)。采用结扎左冠状动脉前降支30 min,再灌注120 min的方法制备大鼠心肌缺血再灌注损伤模型。RG组于心肌缺血前1 h时腹腔注射RGFP96610 mg/kg。于再灌注120 min时分离右侧颈内动脉取血,采用ELISA法检测血清乳酸脱氢酶(LDH)、肌酸激酶(CK-MB)、肌酐(Cr)和尿素氮浓度;取部分肾组织,观察病理学结果,进行肾小管损伤评分,Western blot法检测HDAC3、沉默信息调节因子1(SIRT1)和IL-1β表达水平。结果与S组比较,I/R组血清LDH和CK-MB、Cr、尿素氮浓度和肾小管损伤评分升高,HDAC3和IL-1β表达上调,SIRT1表达下调(P<0.05);与I/R组比较,RG组血清LDH、CK-MB、Cr、尿素氮浓度和肾小管损伤评分降低,HDAC3和IL-1β表达下调,SIRT1表达上调(P<0.05)。结论HDAC3表达上调参与了心肌缺血再灌注诱发糖尿病大鼠肾损伤的过程。Objective To evaluate the role of histone deacetylase 3(HDAC3)in renal injury induced by myocardial ischemia-reperfusion(I/R)in diabetic rats.Methods SPF healthy adult male Sprague-Dawley rats,weighing 210-220 g,were used in this study.Diabetes mellitus was induced by intraperitoneal injection of 1%streptozotocin 60 mg/kg.Eighteen diabetic rats were divided into 3 groups(n=6 each)using a random number table method:sham operation group(group S),group I/R and HDAC3 inhibitor RGFP966 group(RG).The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion.RGFP96610 mg/kg was intraperitoneally injected at 1 h before myocardial ischemia in group RG.The right internal carotid artery was isolated at 120 min of reperfusion for measurement of serum lactate dehydrogenase(LDH),creatine kinase-MB(CK-MB),creatinine(Cr)and urea nitrogen concentrations.Renal tissues were obtained for examination of the pathological changes and for determination of the expression of HDAC3,silent information regulator 1(SIRT1)and interleukin-1β(IL-1β).The damage to the renal tubules was scored.ResultsCompared with S group,the serum LDH,CK-MB,Cr and urea nitrogen concentrations and renal tubular damage score were significantly increased,the expression of HDAC3 and IL-1βwas up-regulated,and the expression of SIRT1 was down-regulated in group I/R(P<0.05).Compared with group I/R,the serum LDH,CK-MB,Cr and urea nitrogen concentrations and renal tubular damage score were significantly decreased,the expression of HDAC3 and IL-1βwas down-regulated,and the expression of SIRT1 was up-regulated in group RG(P<0.05).Conclusion Up-regulated expression of HDAC3 is involved in renal injury induced by myocardial I/R in diabetic rats.

关 键 词：蛋白脱乙酰基酶类 糖尿病 心肌再灌注损伤 急性肾损伤 

分 类 号：R28[医药卫生—中药学]