p38丝裂原活化蛋白激酶参与脓毒症小鼠血小板减少的调控  

Regulation of p38 mitogen-activated protein kinase signal pathway-mediated thrombocytopenia in septic mice

作　　者：朱鹏程[1] 吴少梅[2] 程星[2] 陈丁[2] 薛寅凯 陈路佳[2] 窦东伟[2] 郑海[2] 陈立波[2] 程平[2] 

机构地区：[1]江苏省常州市第二人民医院重症医学科,常州213003 [2]华中科技大学同济医学院附属协和医院急诊外科,武汉430022

出　　处：《中华实验外科杂志》2016年第10期2327-2329,共3页Chinese Journal of Experimental Surgery

基　　金：湖北省自然科学基金（2014CFB992）

摘　　要：目的 探讨p38丝裂原活化蛋白激酶（p38MAPK）是否参与脓毒症小鼠血小板减少的调控.方法 应用腹腔注射致死剂量脂多糖（LPS）制造小鼠脓毒症模型.60只小鼠随机分为对照组、脓毒症组（LPS组）和p38抑制剂组（SB203580处理组）.连续4d检测外周血血小板数量和白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）表达量：于造模后24h采血观察血小板形态,检测血小板磷酸化p38MAPK表达,取小鼠肺组织行免疫组织化学观察血小板肺滞留.结果 脓毒症小鼠外周血中IL-6、TNF-α明显升高,血小板肿胀、变形,呈活化状态,伴磷酸化p38MAPK （p-p38MAPK）表达量显著增加（条带灰度比为0.603 1±0.032 5,P＜0.01）,及肺组织中大量血小板滞留（平均吸光度值为206.18 ±5.14,P＜0.05）.结论 p38MAPK是血小板活化的重要信号通路,抑制p38MAPK可以减少血小板活化及肺组织血小板滞留,预防脓毒症血小板减少.Objective To discuss whether p38 mitogen-activated protein kinase （p38MAPK） signal pathway participates in the modulation of thrombocytopenia in septic mice.Methods Mice models of sepsis were established by intraperitoneal injection of lipopolysaccharide （LPS） in the lethal dose.Sixty mice were randomly divided into three groups：control group,sepsis group and the p38MAPK inhibitor group （SB203580 treatment group）.Platelet counts,and the expression of interleukin （IL）-6 and tumor necrosis factor-α （TNF-α） were detected continuously in the first four days.Twenty-four h after the injection of LPS,the morphological changes in platelets were observed,the expression of p-p38MAPK was detected,and platelet sequestration in the lung was examined through immunohistochemistry.Results The concentrations of IL-6 and TNF-α were higher in LPS group than in control group.In LPS group,large number of swelling and deformative platelets were observed,showing significant status of activation.The expression of phosphorylated p38MAPK （p-p38MAPK,ratio of band density was 0.603 1 ±0.032 5,P 〈0.01） in platelets and sequestration of platelets in the lung increased obviously in LPS group （mean density value was 206.18 ± 5.14,P 〈 0.05）.Conclusion p38MAPK may play an important role in the activation of platelets.Inhibition of p38MAPK can reduce activation of platelets,sequestration of platelets in the lung,and finally prevent thrombocytopenia of septic mice.

关 键 词：脓毒症 血小板 P38丝裂原活化蛋白激酶 

分 类 号：R459.7[医药卫生—急诊医学]