Chen Xu-lin, Xia Zhao-fan, Wei Duo, Ben Dao-feng, Wang Guang-qing, Tang Hong-tai
Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, P.R. China.
Zhonghua Shao Shang Za Zhi. 2004 Oct;20(5):262-4.
To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the production of the proinflammatory factors such as tumor necrosis factor (TNF-alpha) and interleukin 1beta (IL-1beta) in lungs and in the pulmonary endothelial cell injury in severely scalded rats.
Forty eight adult healthy SD rats were randomly divided into three groups with 16 rats in each group, i.e. sham, burn and burn with SB203580 treatment groups. The changes in the TNF-alpha and IL-1beta contents in serum and bronchoalveolar lavage fluid (BALF), the von Willebrand factor (vWF) contents in plasma and pulmonary microvessels and pulmonary activating protein (AP-1) activity were determined at 24 postburn hours (PBH).
Compared with those in sham group, the TNF-alpha and IL-1beta contents in serum and BALF and the vWF content in plasma (194.2% +/- 28.3% vs 93.2% +/- 14.3%) at 24 PBH in burn group increased significantly (P < 0.01), whereas vWF content in pulmonary microvessel decreased obviously (1.1 +/- 0.3 vs 3.3 +/- 0.4, P < 0.01). In addition, the pulmonary AP-1 activity also increased at 24 PBH. Nevertheless, all the above indices improved obviously in burn with SB203580 (inhibitor of p38 MAPK signal transduction pathway) treatment group when compared with those in burn group.
AP-1 might mediate the production of proinflammatory factors, such as TNF-alpha and IL-1beta in lungs leading to pulmonary vascular endothelial injury, after being activated by activated p38 MAPK.
探讨p38丝裂原活化蛋白激酶（MAPK）信号转导通路在严重烫伤大鼠肺组织中促炎因子如肿瘤坏死因子（TNF-α）和白细胞介素1β（IL-1β）产生及肺血管内皮细胞损伤中的作用。
48只成年健康SD大鼠随机分为3组，每组16只，即假伤组、烫伤组和烫伤+SB203580治疗组。于伤后24小时（PBH）测定血清和支气管肺泡灌洗液（BALF）中TNF-α和IL-1β含量、血浆和肺微血管中血管性血友病因子（vWF）含量以及肺组织活化蛋白（AP-1）活性。
与假伤组相比，烫伤组伤后24小时血清和BALF中TNF-α和IL-1β含量以及血浆中vWF含量（194.2%±28.3%对93.2%±14.3%）显著升高（P<0.01），而肺微血管中vWF含量明显降低（1.1±0.3对3.3±0.4，P<0.01）。此外，伤后24小时肺组织AP-1活性也升高。然而，与烫伤组相比，烫伤+SB203580（p38 MAPK信号转导通路抑制剂）治疗组上述各项指标均明显改善。
活化的p38 MAPK激活AP-1后，AP-1可能介导肺组织中TNF-α和IL-1β等促炎因子的产生，导致肺血管内皮损伤。
