SAHA对2型糖尿病大鼠舒芬太尼后处理心肌保护作用的影响  

Effect of SAHA on sufentanil postconditioning-induced cardioprotection in rats with type 2 diabetesmellitus

作　　者：董森林[1] 顾尔伟[1] 鲁显福[1] 张雷[1] 陈满丽[1] 赵仙雅 

机构地区：[1]安徽医科大学第一附属医院麻醉科,合肥市230022

出　　处：《中华麻醉学杂志》2016年第10期1187-1192,共6页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金专项主任基金（81341014）;安徽高校省级自然科学研究重点项目（KJ2013A161）

摘　　要：目的探讨辛二酰苯胺异羟肟酸（SAHA）对2型糖尿病大鼠舒芬太尼后处理心肌保护作用的影响。方法SPF级雄性sD大鼠，体重250-300g，5～6周龄，采用高脂饲料喂养4周联合腹腔注射1％链脲佐菌素35mg／kg的方法制备2型糖尿病模型。取模型成功制备的大鼠40只，采用随机数字表法分成5组（n=8）：假手术组（T2DM—S组）、缺血再灌注组（T2DM-I／R组）、舒芬太尼后处理组（T2DM—SP组）、SAHA组（T2DM—SA组）、SAHA＋舒芬太尼后处理组（T2DM—SASP组）。T2DM—SA组和T2DM—SASP组于术前连续5d腹腔注射SAHA25mg／kg，1次／d。制备心脏Langendorff离体灌注模型，采用全心停止灌注30min，再灌注120min的方法制备缺血再灌注损伤模型。于平衡灌注30min、再灌注30、60和120min时记录左心室发展压（LVSP）、HR、左心室内压最大上升速率（＋dp／dtmax）和左心室内压最大下降速率（-dp／dtmax）。再灌注120min时确定左心室体积（LVM）和梗死区体积（IS），计算IS／LVM比率，采用Westernblot法检测心肌糖原合成酶激酶-3β（GSK-3β）和p-GSK-3β的表达。结果与T2DM-S组比较，T2DM-I／R组LVSP、HR、＋dp／dtmax、-dp／dtmax降低，Is和IS／LVM比率升高，心肌p-GSK-3β表达下调（P〈0．05）；与T2DM—I／R组比较，T2DM—SASP组＋dp／dtmax和-dp／dtmax升高，Is和IS／LVM比率降低，心肌p-GSK-3β表达上调（P〈0．05），T2DM—SA组和T2DM-sP组各测定指标差异无统计学意义（P〉0．05）；与T2DM—SP组比较，T2DM—SASP组＋dp／dtmax和-dp／dtmax升高，Is和IS／LVM比率降低，心肌p-GSK-3β表达上调（P〈0．05）。结论SAHA可在一定程度上改良舒芬太尼后处理对2型糖尿病大鼠的心肌保护效应。Objective To investigate the effect of suberoylanilide hydroxamic acid （SAHA） on sufentanil posteonditioning-induced cardioprotection in rats with type 2 diabetes mellitus （T2DM）. Meth- ods Male SPF Sprague-Dawley rats, weighing 250-300 g, aged 5-6 weeks, were used in the study. T2DM was induced by high-fat diet （4 weeks） and intraperitoneal 1% streptozotocin 35 mg/kg, and con- firmed by fasting blood glucose level≥ 16.7 mmol/L. Forty rats with T2DM were divided into 5 groups （n= 8 each） using a random number table： sham operation group （grou T2DM-S）; ischemia-reperfusion group （group T2DM-I/R）; sufentanil postconditioning group （group T2DM-SP）; SAHA group （group T2DM-SA）; SAHA plus sufentanil postconditioning group （group T2DM-SASP ）. In T2DM-SA and T2DM-SASP groups, SAHA 25 mg/kg was injected intraperitoneally once a day for 5 consecutive days be- fore operation. Their hearts were excised and retrogradely perfused in a Langendorff apparatus. The hearts were subjected to 30 min of global ischemia followed by 120 min of reperfusion to establish the model of is-chemia/reperfusion injury. At 30 min of equilibration and 30, 60 and 120 min of reperfusion, the left ven- tricular systolic pressure （LVSP） , heart rate （HR）, and the maximum rate of increase and decrease of ventricular pressure （＋dp/dtmax ） were recorded. At 120 min of reperfusion, the left ventricular mass （LVM） and infarct size （IS） were measured, and IS/LVM ratio was calculated. The expression of glyco- gen synthesis kinase 3β （GSK-3β） and phosphorylated GSK-3β （p-GSK-3β） in the myocardium was de- tected by Western blot. Results Compared with group T2DM-S, the LVSP, HR and ±dp/dt were sig- nificantly decreased, the IS and IS/LVM ratio were significantly increased, and the expression of myocardi- al p-GSK-3β was significantly down-regulated in group T2DM-I/R （P〈0.05）. Compared with group T2DM- I/R, the ±dp/dtm,x was significantly increased, the IS and IS/LVM ratio were si

关 键 词：羟肟酸类 糖尿病  2型 舒芬太尼 心肌再灌注损伤 

分 类 号：R614[医药卫生—麻醉学]