高迁移率族蛋白-1、糖基化终产物受体及Toll样受体-4通路对爆震伤致大鼠急性肺损伤影响研究  

Effects of HMGB-1,RAGE and TLR-4 pathway on acute lung injury induced by blast in rats

作　　者：佟昌慈 柳云恩[1] 张玉彪[1] 施琳[1] 丛培芳[1] 刘颖[1] 史秀云[1] 金红旭[1] 侯明晓[1] 

机构地区：[1]沈阳军区总医院急诊医学部全军重症(战)创伤救治中心实验室辽宁省重症创伤和器官保护重点实验室,辽宁沈阳110016

出　　处：《创伤与急危重病医学》2017年第4期198-204,共7页Trauma and Critical Care Medicine

摘　　要：目的探讨高迁移率族蛋白(HMGB)-1、糖基化终产物受体(RAGE)及Toll样受体(TLR)-4通路对爆震伤致大鼠急性肺损伤的调控机制。方法选取40只SD大鼠,10只纳入对照组;其余30只在建立爆震伤致大鼠急性肺损伤模型后,分别纳入6 h组、12 h组、24 h组。ELISA检测大鼠血清炎症因子HMGB-1、白细胞介素(IL)-1α、IL-8;Real Time PCR、Western Blot及免疫荧光检测大鼠肺组织炎症因子HMGB-1、IL-1α、IL-8及通路相关蛋白RAGE、TLR-4、p38丝裂原活化蛋白激酶(MAPK)、两面神激酶(JAK)-2、信号传导及转录激活因子(STAT)-3。结果 ELISA结果显示,与对照组比较,12 h组、24 h组HMGB-1与IL-1α表达增高,12 h组表达量最高;6 h组、12 h组IL-8表达增高,12 h组表达量最高(P<0.05)。Real Time PCR、Western Blot及免疫荧光结果显示,与对照组比较,12 h组、24 h组HMGB-1与IL-1α表达增高,12 h组表达量最高;6 h组、12 h组IL-8表达增高,12 h组表达量最高;12 h组RAGE表达增高;12 h组、24 h组TLR-4、p38 MAPK表达增高,12 h组表达量最高;6 h组、12 h组、24 h组JAK-2、STAT-3表达增高,12 h组表达量最高(P<0.05)。结论爆震伤致大鼠急性肺损伤诱导HMGB-1释放,结合RAGE与TLR-4受体,激活p38 MAPK与JAK/STAT通路,促进炎症因子IL-1α、IL-8的作用,调节炎症反应。Objective To investigate the mechanism of high mobility group protein-1 （ HMGB-1 ）, receptor for advanced gly- cation end products（RAGE） and Toll-like receptor-4 （TLR-4）pathway on acute lung injury induced by blast in rats. Meth- ods There were 40 SD rats were selected,10 rats were divided into the control group;the other 30 rats were divided into the 6 hours group, 12 hours group and 24 hours group after the establishment of rat model with acute lung injury induced by blast. The levels of serum HMGB-1, IL-lα and IL-8 were detected by ELISA. The expression of HMGB-1, IL-lα, IL-8, RAGE,TLR-4, p38 MAPK, JAK-2 and STAT-3 in lung tissue were detected by Western Blot, Real Time PCR and immuno- fluorescence. Results The result of ELISA showed that, compared with the control group, the expression of HMGB-I and IL-lα in 12 hours group and 24 hours group both increased,and the level reached the highest in 12 hours group;the expres- sion of IL-8 in 6 hours group and 12 hours group increased, and the level reached the higher in 12 hours group（P 〈 0.05 ）. The results of Western Blot, Real Time PCR and immunofluorescence showed that, compared with the control group,the ex-pression of HMGB-1 and IL-lcdn 12 hours group and 24 hours group increased, and the level reached the highest in 12 hours group;the expression of IL-8 in 6 hours and 12 hours increased, and the level reached the highest in 12 hours group;the expression of RAGE in 12 hours group increased;the expression of TLR-4 and p38 MAPK in 12 hours group and 24 hours group increased,and the level reached the highest in 12 hours group;the expression of JAK-2 and STAT-3 in 6 hours, 12 hours and 24 hours groups increased,and the level reached the highest in 12 hours group（P 〈0. 05）. Conclusion The acute lung injury induced by blast injury in rats can promote the release of inflammatory factors and promote the inflammatory re- sponse by promoting the release of HMGB-1 ,binding to RAGE and TLR-4,activating p38 MAPK and JAK/STAT pathway.

关 键 词：爆震伤 急性肺损伤 大鼠 高迁移率族蛋白 糖基化终产物受体 Toll样受体 

分 类 号：R631[医药卫生—外科学]