Role of p38MAPK signaling pathway in up-regulation of heme oxygenase-1 expression during hemorrhagic shock and resuscitation-induced acute lung injury in mice
10.3760/cma.j.issn.0254-1416.2010.10.028
- VernacularTitle: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
- Author:
Chang CHEN
;
Zongze ZHANG
;
Jia ZHAN
;
Mian PENG
;
Yanlin WANG
- Publication Type:Journal Article
- Keywords:
p38 Mitogen-activated protein kinases;
Heme oxygenase-1;
Shock,hemorrhagic;
Respiratory distress syndrome,adult
- From:Chinese Journal of Anesthesiology
2010;30(10):1247-1249
- CountryChina
- Language:Chinese
-
Abstract:
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.
