作　　者： (张瑜）; (孟宇）; (郭素倩）; (乌兰）; (赵亓）; (宋程程）; (于泳浩）; (王国林）;

机构地区： 天津医科大学总医院麻醉科,天津市麻醉学研究所,300052

出　　处： 《中华麻醉学杂志》 2017年第7期888-890,共3页

摘　　要： 目的 评价右美托咪定对脓毒症大鼠肝损伤时程序性坏死的影响.方法 SPF级成年雄性SD大鼠18只,体重200- 220 g,采用随机数字表法分为3组（n=6）：假手术组（SH-组）、脓毒症组（SEP组）和右美托咪定组（DEX组）.SEP组和DEX组采用盲肠结扎穿孔法制备大鼠脓毒症模型.DEX组术前1h时尾静脉注射右美托咪定5 μg/kg.于术后6h时尾静脉取血样,测定血清AST和ALT的浓度,然后处死大鼠取肝组织,采用化学荧光法检测ROS水平,采用Western blot法测定受体相互作用蛋白1（RIP1）、受体相互作用蛋白3（RIP3）、混合系列蛋白激酶样结构域（MLKL）、高迁移率族蛋白1（HMGB1）和动力相关蛋白1（Drp1）的表达.结果 与SH组比较,SEP组和DEX组血清AST和ALT的浓度升高,肝组织RIP1、RIP3、MLKL、HMGB1和Drp1的表达上调,ROS水平升高（P〈0.05）;与SEP组比较,DEX组血清AST和ALT的浓度下降,肝组织RIP1、RIP3、MLKL、HMGB1和Drpl的表达下调,ROS水平降低（P〈0.05）.结论 右美托咪定减轻脓毒症大鼠肝损伤的机制可能与抑制程序性坏死有关. Objective To evaluate the effect of dexmedetomidine on necroptosis during liver injury in septic rats.Methods Eighteen SPF adult male Sprague-Dawley rats,weighing 200-220 g,were divided into 3 groups （n=6 each） using a random number table：sham operation group （group SH）,sepsis group （group SEP） and dexmedetomidine group （group DEX）.Sepsis was induced by cecal ligation and puncture in chloral hydrate-anesthetized rats in SEP and DEX groups.Dexmedetomidine 5 μg/kg was injected via the caudal vein at 1 h before operation in group DEX.Blood samples were collected from the caudal vein at 6 h after operation for determination of serum aspartate amino-transferase （AST） and alanine aminotransferase （ALT） concentrations.The rats were then sacrificed and livers were removed for determination of the level of reactive oxygen species （ROS） in liver tissues （using chemiluminescence assay） and expression of receptor-interacting protein 1 （RIP1）,RIP3,mixed lineage kinase domain-like （MLKL）,high-mobility group box 1 protein （HMGB1） and dynamin-related protein 1 （Drpl） in liver tissues （by Western blot）.Results Compared with group SH,the serum AST and ALT concentrations were significantly increased,the expression of RIP1,RIP3,MLKL,HMGB1 and Drpl in liver tissues was up-regulated,and the level of ROS in liver tissues was increased in SEP and DEX groups （P〈0.05）.Compared with group SEP,the serum AST and ALT concentrations were significantly decreased,the expression of RIP1,RIP3,MLKL,HMGB1 and Drp1 in liver tissues was down-regulated,and the level of ROS in liver tissues was decreased in group DEX （P〈0.05）.Conclusion The mechanism by which dexmedetomidine attenuates liver injury may be related to inhibition of necroptosis in septic rats.

关 键 词： 右美托咪啶 脓毒症 肝 坏死