p38MAPK在百草枯中毒致大鼠急性肺损伤中的作用研究  

Role of p38MAPK in the acute lung injury induced by paraquat in rats

作　　者：陈娇[1] 钱晓明[2] 任艺[1] 孙兆瑞[1] 孙宝迪[1] 邵旦兵[1] 刘红梅[1] 许宝华[1] 唐文杰[1] 张炜[1] 杨志洲[1] 聂时南[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)急救医学科,江苏南京210002 [2]南京大学医学院临床学院(南京军区南京总医院)老年干部二科,江苏南京210002

出　　处：《中国急救医学》2014年第2期183-186,I0002,共5页Chinese Journal of Critical Care Medicine

基　　金：南京军区122工程重点培养对象资助项目（JQZD200905）;南京军区南京总医院青年基金课题（2011030）

摘　　要：目的 探讨p38丝裂原活化蛋白激酶（p38MAPK）在百草枯致大鼠急性肺损伤中作用的研究.方法 96只SD大鼠以数字随机法随机分为生理盐水组（NS）、PQ中毒组（PQ组）、抑制剂干预对照组（PQ＋SB组）和抑制剂对照组（NS＋SB组）,每组各24只,通过比较肺组织的干湿比（W/D）、肺组织病理学变化、肺泡灌洗液中炎症因子IL-1β和TNF-α变化,用Westernblot检测各组大鼠肺组织中p38MAPK、p-p38MAPK的变化表达量,并用p38MAPK的特异性抑制剂SB203580干预,阻断p38MAPK磷酸化过程,进一步确定p38MAPK与肺组织炎症反应等的相关性.结果 PQ组p-p38MAPK表达量明显高于NS组,PQ＋SB组较PQ组表达量有所下降,PQ＋SB组肺W/D在1、3、5 d均低于PQ组（P〈0.01）,在7 d两组比较差异无统计学意义（P〉0.05）;PQ＋SB组肺组织中TNF-α、IL-1β水平明显低于PQ组（P〈0.01）,肺组织病理学变化也较PQ组有所改善.结论 p38MAPK信号通路参与介导了百草枯致大鼠急性肺损伤的炎症反应过程,用p38MAPK抑制剂SB203580干预后可改善肺组织的炎症反应.Objective To investigate the role of p38MAPK in the acute lung injury induced by paraquat （PQ） in rats. Methods 96 SD rats were randomly divided into normal saline group （NS） group, PQ poisoning group （PQ）, p38MAPK inhibitor intervention control group （PQ ＋ SB） and inhibitor control group （NS ＋ SB） with 24 rats in each group. Lung weight ratio （wet to dry, W/D）, lung tissue pathological change, changes of the TNF -α, IL - 1β in alveolar lavage fluid and the expression of the p38MAPK, p - p38MAPK in lung tissue were compared among the groups. A specific p38MAPK inhibitor SB203580 was used to block the p38MAPK phosphorylation process, and to further determine whether p38MAPK was involved in the lung tissue inflammation caused by PQ. Results p38MAPK expression in PQ group was significantly higher than that in NS group, but was partially decreased in PQ ＋SB group. Lung W/D in 1 d, 3 d, 5 d were lower in PQ ＋SB group than those in PQ group （P 〈 0.01 ）, but they had no significant difference in 7 d （ P 〉 0.05 ）. PQ ＋ SB group rats expressed lower level of TNF - α and IL - 1β in lung tissue when compared to PQ poisoning group （ P 〈 0.01 ）. Similarly, the pathological changes in PQ ＋ SB group were also improved than those in PQ group. Conclusion p38MAPK is involved in mediating the inflammatory response process of the acute lung injury induced by PQ in rats, and using the p38MAPK inhibitor SB203580 can improve the lung tissue inflammation.

关 键 词：p38丝裂原活化蛋白激酶(p38MAPK) 百草枯中毒 急性肺损伤 炎症反应 

分 类 号：R651.2[医药卫生—外科学]