核因子-κB介导脂多糖诱导急性肺损伤大鼠高迁移率族蛋白B1的表达  

NF-κB mediatesthe expression of HMGB1 in ALI rats induced by lipopolysaccharide

作　　者：高鹏飞[1] 张锋[1] 程彬彬[2] 刘功俭[1] 

机构地区：[1]徐州医学院麻醉学重点实验室,221002 [2]徐州医学院华方学院临床医学系

出　　处：《临床麻醉学杂志》2015年第3期278-281,共4页Journal of Clinical Anesthesiology

摘　　要：目的探讨核因子（NF）-κB在脂多糖诱导大鼠急性肺损伤过程中对肺组织高迁移率族蛋白B1（HMGB1）表达的影响。方法采用腹腔注射脂多糖（LPS）致大鼠脓毒症急性肺损伤模型。取健康SPF级雄性SD大鼠72只,体重180-220g,采用随机数字表法,分为对照组（C组,n=6）、急性肺损伤组（L组,n=30）、吡咯烷二硫代氨基甲酸盐（PDTC）溶剂对照组（P组,n=6）,PDTC治疗组（LP组,n=30）。各组分别给予腹腔注射磷酸盐缓冲液（PBS）（C和P组）或LPS（L和LP组）;P组和LP组在PBS或LPS注射前15min,给予腹腔注射PDTC 100mg/kg。C组和P组腹腔注射PBS后的16h,L组和LP组注射LPS后的16h后各取6只大鼠检测其肺湿/干重比（W/D）;C组和P组腹腔注射PBS后的16h,L组和LP组注射LPS后的4h（T1）、8h（T2）、16h（T3）、24h（T4）和48h（T5）时各取6只大鼠经处理后采用ELISA法检测支气管肺泡灌洗液（BALF）中髓过氧化物酶（MPO）和白细胞介素6（IL-6）水平,Western blot法检测肺组织HMGB1的表达水平,苏木精-伊红（HE）染色观察肺组织的病理变化。结果与C组比较,L组肺组织W/D、BALF中MPO和IL-6水平明显升高（P〈0.01）,病理切片显示严重肺组织损伤,T2-T4时肺组织中HMGB1的表达水平明显升高（P〈0.05）;使用PDTC治疗后,与L组比较,肺组织W/D、BALF中MPO和IL-6水平明显降低（P〈0.01）,病理示肺损伤程度明显减轻;T2-T4时肺组织HMGB1表达水平明显降低（P〈0.05）。结论在脂多糖诱导急性肺损伤中,被激活的NF-κB通过介导晚期炎症因子HMGB1的表达来参与急性肺损伤的发生与发展过程。Objective To investigate the effects of NF-κB on the expression of high mobility group protein 1（HMGB1）in lipopolysaccharide induced acute lung injury rats.Methods LPS（5mg/kg,ip）induced acute lung injury model was used in our experiment,72 healthy male Sprague-Dawley rats,weighing180-220 g,were randomly divided into four groups：Control group（group C,n=6）received an intraperitoneal injection of PBS;Acute lung injury group（group L,n=30）received LPS injection（5mg/kg,i.p.）;PDTC solvent control group（group P,n=6）received PDTC injection（100mg/kg,i.p.）and PDTC treatment group（group LP,n=30）received PDTC（100mg/kg,i.p.）15min before LPS administration.The lung wet/dry weight ratio（W/D）were analyzed,the level of MPO and IL-6in bronchoalveolar lavage fluid was detected by ELISA,hitophathological changes in lung tissue were observed by HE staining and the expression of HMGB1 was analyzed by Western blot 4,8,16,24 and 48hafter the injection of LPS in groups L and LP.Results W/D,MPO and IL-6in lung tissue significantly increased in group L（P〈0.01）.The hematoxylin-eosin staining of lung tissues showed that the inhibitor of NF-κB significantly attenuated the pulmonary inflammatory responses and W/D induced by LPS.In addition,PDTC can also inhibit the release of inflammatory cytokines such as MPO and IL-6,and reduce the mortality rate of rats in group L（P〈0.05）.Furthermore,Western blot analysis showed that PDTC administration can inhibit the expression of HMGB1 in lung tissues（P〈0.05）.Conclusion The activation of NF-κB may participate in the progress of acute lung injury via promoting the expression of HMGB1.

关 键 词：核因子ΚB 脂多糖 急性肺损伤 吡咯烷二硫代氨基甲酸盐 高迁移率族蛋白1 

分 类 号：R614[医药卫生—麻醉学]