P38MAPK信号通路在失血性休克复苏诱发急性肺损伤小鼠HO-1表达上调中的作用  

Role of p38MAPK signaling pathway in up-regulation of heme oxygenase-1 expression during hemorrhagic shock and resuscitation-induced acute lung injury in mice

作　　者：陈畅[1] 张宗泽[1] 詹佳[1] 彭勉[1] 王焱林[1] 

机构地区：[1]武汉大学中南医院麻醉科,430071

出　　处：《中华麻醉学杂志》2010年第10期1247-1249,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81000318）;武汉大学青年教师资助项目（4101003）

摘　　要：目的 探讨p38分裂原激活蛋白激酶（p38MAPK）信号通路在失血性休克复苏诱发急性肺损伤小鼠血红素加氧酶1（HO-1）表达上调中的作用.方法 SPF级野生型小鼠C3H/HeN32只32只,10～12周龄,体重20～25 g,随机分为4组（n=8）,假手术组（S组）：只进行手术操作;失血性休克复苏组（HSR组）：股动脉放血,至MAP为40 mm Hg,通过放血和回输血液维持MAP 35～45mmHg,60 min后回输全部血液和等失血量的乳酸钠林格氏液复苏;FR167653组（FR组）：静脉注射p38MAPK抑制剂FR167653 5 mg/kg;FR＋HSR组：于放血前30 min静脉注射FR167653 5 mg/kg.复苏后6 h处死小鼠,取肺组织,观察病理学结果,并进行病理学评分,计算肺湿/干重比,检测肺组织髓过氧化物酶（MPO）、IL-10、IL-6和HO-1水平以及p38MAPK的激活水平.结果 与S组比较,HSR组肺组织病理学评分、肺湿/干重比、MPO、IL-6、IL-10、HO-1和p38MAPK的激活水平升高,HSR＋FR组肺组织病理学评分、肺湿/干重比和HO-1表达水平升高（P＜0.01）,FR组上述指标差异无统计学意义（P＞0.05）;与HSR组比较,HSR＋FR组肺组织病理学评分、肺湿/干重比、MPO、IL-6、IL-10、HO-1和p38 MAPK激活水平降低（P＜0.01）.结论 p38MAPK信号通路介导了失血性休克复苏诱发急性肺损伤小鼠HO-1的表达上调.Objective To evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 （HO-1） expression during hemorrhagic shock and resuscitation （HSR）-induced acute lung injury （ALI） in mice. Methods Thirty-two C3H/HeN （wild-type） mice, aged 10-12 weeks, weighing 20-25 g, were randomly divided into 4 groups （n = 8 each）： sham operation group （group S）; group HSR; FR167653 （a p38MAPK inhibitor） group （group FR） and FR167653 ＋ HSR group （group FR ＋ HSR）. HSR was induced according to the methods described by Ayala et al. MAP was reduced to 35-45 mm Hg and maintained for 60 min.Then the animals were resuscitated with transfusion of the shed blood and lactated Ringer＇s solution equivalent to the volume of shed blood. FR167653 5 mg/kg was injected intravenosly in group FR. FR167653 5 mg/kg was injected intravenously 30 min before blood-letting in group FR ＋ HSR. The animals were sacrificed by exsanguination at 6 h after resuscitation. The lungs were immediately removed for microscopic examination. The W/D lung weight ratio was calculated and the levels of myeloperoxidase （MPO）, IL-10, IL-6 and HO-1 and activated p38MAPK were determined （by ELISA）.Results Compared with group S, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and the level of activated p38MAPK were significantly increased in group HSR, the pathological score, W/D ratio and the level of HO-1 were significantly increased in group HSR ＋ FR （ P 〈 0.01） .Compared with group HSR, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and activated p38MAPK were significantly decreased in group HSR ＋ FR （ P 〈 0.01 ）. Conclusion p38MAPK signaling pathway mediates the up-regulation of HO-1 expression during HSR-induced ALI in mice.

关 键 词：P38丝裂原活化蛋白激酶类 血红素加氧酶-1 休克 出血性 呼吸窘迫综合征 成人 

分 类 号：R605.971[医药卫生—急诊医学]