程序性坏死在大鼠肠缺血再灌注损伤中的作用  

Role of necroptosis in intestinal ischemia-reperfusion injury in rats

作　　者：杨文静[1] 温仕宏[1] 凌逸虹[2] 刘家欣[1] 沈建通[1] 李云胜[1] 刘克玄[1] 

机构地区：[1]中山大学附属第一医院麻醉科,广州市510080 [2]中山大学肿瘤防治中心病理科

出　　处：《中华麻醉学杂志》2014年第12期1468-1470,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81171847）;国家自然科学基金青年科学基金（81301622,81101407）

摘　　要：目的 评价程序性坏死在大鼠肠缺血再灌注损伤中的作用.方法 健康雄性SD大鼠32只,体重200-220 g,采用随机数字表法,将其分为4组（n=8）：假手术组（Sham组）、肠缺血再灌注组（I/R组）、程序性坏死特异性抑制剂Necrostatin-1组（Nec-1组）和溶剂二甲基亚砜组（DMSO组）.采用夹闭肠系膜上动脉1h再灌注24 h的方法制备肠缺血再灌注损伤模型.Sham组仅分离血管;Nec-1组及DMSO组分别于夹闭肠系膜上动脉前30 min时腹腔注射Necrostatin-1 1.0 mg/kg或等容量二甲基亚砜.于再灌注24 h时取肠组织,观察肠粘膜形态学并行Chiu评分,开胸经心尖取血样2ml,检测血清二胺氧化酶（DAO）活性.采用Western blot法检测肠粘膜组织活化的cmpase-3蛋白和受体相互作用蛋白1（RIP1）的表达水平.结果 与Sham组比较,I/R组、DMSO组及Nec-1组Chiu评分和血清DAO活性升高,肠粘膜组织活化的caspase-3蛋白和RIP1蛋白表达上调（P＜0.01）;与I/R组和DMSO组比较,Nec-1组Chiu评分和血清DAO活性降低,肠粘膜组织RIP1蛋白表达下调（P＜0.05）,活化的caspase-3蛋白表达差异无统计学意义（P＞0.05）.结论 程序性坏死参与了大鼠肠缺血再灌注损伤.Objective To evaluate the role of necroptosis in intestinal ischemia-reperfusion （I/R） injury in rats.Methods Thirty-two healthy male Sprague-Dawley rats,weighing 200-220 g,were randomly assigned into 4 groups （n =.8 each） using a random number table：sham operation group （Sham group）,I/R group,necroptosis inhibitor necrostatin-1 group （Nec-1 group） and solvent dimethyl sulfoxide （DMSO） group （group DMSO）.Intestinal I/R injury was produced by clamping the superior mesenteric artery for 1 h followed by 24 h reperfusion in rats anesthetized with chloral hydrate.Necrostatin-1 1.0 mg/kg was administered intraperitoneally at 30 min before occlusion in Nec-1 group,while the equal volume of DMSO was given instead in group DMSO.The rats were sacrificed at 24 h of reperfusion and the intestinal tissues were removed for microscopic examination.Intestinal damage was assessed and scored according to Chiu.Blood samples were taken for determination of serum diamine oxidase （DAO） activity.The expression of activitied caspase-3 and receptor-interacting protein 1 （RIP1） in intestinal tissues was detected using Western blot.Results Compared with Sham group,Chiu＇s score,serum DAO activity,and the expression of activitied caspase-3 and RIP1 was up-regulated in I/R,DMSO and Nec-1 groups.Compared with I/R and DMSO groups,Chiu＇s score and DAO activity were significantly decreased,the expression of RIP1 was down-regulated,and no significant change was found in the expression of activitied caspase3 in group Nec-1.Conclusion Necroptosis is involved in intestinal I/R injury in rats.

关 键 词：肠 再灌注损伤 细胞死亡 

分 类 号：R574[医药卫生—消化系统]