程序性坏死在脓毒症大鼠肝脏损伤中的作用  

Role of necroptosis in liver injury in septic rats

作　　者：张瑜[1] 孟宇[2] 郭素倩 乌兰[1] 赵亓[1] 于泳浩[1] 王国林[1] 

机构地区：[1]天津医科大学总医院麻醉科天津市麻醉学研究所,300052 [2]天津医科大学总医院重症监护室,300052

出　　处：《中华麻醉学杂志》2017年第6期748-750,共3页Chinese Journal of Anesthesiology

摘　　要：目的评价程吩性坏死征脓毒症大鼠肝肌损伤中的作用。方法SPF级健康雄性SD大鼠24只，体重200～220g，6～8周龄，采用随机数字表法分为3组（n=8）：假手术组（Sh组）、脓毒症组（Sep组）和程序性坏步匕特砰性抑制剂necrostatin-1组（N组）。N绀及Sep组采用盲肠结扎穿孔法制备大鼠脓毒症模型，N组于术前1h时静脉注射necrostatin-1 1．0mg／kg，Sep组给予等容戢：甲基亚砜。于术后6h时取肝组织，光镜下观察肝脏形态学，采用化学荧光法检测活性氧（ROS）水平，采用Western1）lot法检测受体棚瓦作用蛋门激酶（RIPK）1、RIPK3、混合系列蛋白激酶样结构域（MLKL）和高迁移率族蛋hl（HMGBl）的表达。结果与sh组比较，Sep组和N组肝绀织ROS水平升高，肝组织RJPK1、RIPK3、MI,KL和HMGB1表达上调（P〈0．05）；与Sep组比较，N组肝组织ROS水平降低，肝组织RIPKl、RIPK3、MLKL和HMGBl表达下调（P〈0．05）。N组肝组织病理学损伤较Sep组减轻。结论程序性坏死参与了脓毒症大鼠肝脏损伤的过程。Objective To evaluate the role of necroptosis in liver injury in septic, rats. Methods Twenty-four SPF healthy male adult Sprague-Dawley rats, weighing 200-220 g, aged 6-8 weeks, were di- vided into 3 groups （n= 8 eat.h） using a random number table： sham operation group （Sh group） , sepsis group （Sep group） and specific neeroptusis inhibitor necrostatin-I group （N group）. Sepsis was induced by cecal ligatiun and puncture in anesthetized rats in N and Sep groups. Neerostatin-1 1.0 mg/kg was intrave- nously injected at 1 h befi）re operation in group N, while the equal volume of dimethyl sulfoxide was given instead in group Sep. Rats were sacrificed at 6 h after operation, and livers were removed for examination of the pathological ctlanges （ with a light microscope） anti for determination of tile level of reactive oxygen spe- cies （ROS） in liver tissues （ by using ehemilurrfinescenee assay） and expression of receptor-interacting pro- tein kinase-I （I{1PKI） , RIPK3, mixed lineage kinase domain-like （MLKL） and high-mobility group box 1 protein （HMGBI） in liver tissues （using Western blot）. Results Compared with Sh group, the ROS level in Liver tissues was significantly increased, and the expression of RIPKI, RIPK3, MLKL and HMGBI in liver lissues was up-regulated in Sep and N groups （P〈0.05）. Compared with Sep group, the ROS level in liver tissues was significantly decreased, and the expression of RIPK1, RIPK3, MLKL and HMGB 1 in liver tissues was down-regulated in group N （P〈0.05）. The pathological changes of liver tissues were significantly attenuated in group N when compared with group Sep. Conclusion Necroptusis is involved in liver injury in septic rats.

关 键 词：脓毒症 肝 坏死 

分 类 号：R459.7[医药卫生—急诊医学]