Zheng De-Yi, Zhou Min, Jin Jiao, He Mu, Wang Yi, Du Jiao, Xiao Xiang-Yang, Li Ping-Yang, Ye Ai-Zhu, Liu Jia, Wang Ting-Hua
Department of Burn and Plastic Surgery, Guizhou Provincial People's Hospital, Guiyang 550002, China.
Institute of Neuroscience, Kunming Medical University, Kunming 650031, China; Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Mediators Inflamm. 2016;2016:9348037. doi: 10.1155/2016/9348037. Epub 2016 Feb 11.
Acute lung injury (ALI) induced by intestinal ischemia/reperfusion (II/R) has high incidence and mortality, in which IL-1β was essential for the full development of ALI. However, the detailed regulating mechanism for this phenomenon remains to be unclear. The purpose of this study was to investigate whether inhibition of P38 MAPK could downregulate the expression of IL-1β to protect lung from acute injury in II/R rats. Here, we found that the level of pulmonary edema at 16 hours after operation (hpo) was obviously enhanced compared to that in 8hpo and sham groups. Immunofluorescent staining demonstrated that IL-1β and P38 MAPK were detected in lung tissues. And rats with II/R have the highest translation level for IL-1β and phosphorylation of P38 MAPK in lung tissues at 16hpo compared with 8hpo and sham groups. Moreover, administration of SB239063, an inhibitor of P38 α and β, could effectively downregulate the expressions of IL-1β and protects lung tissues from injury in II/R rats. Our findings indicate that the inhibition of P38 α and β may downregulate the expression of IL-1β to protect lung from acute injury in II/R, which could be used as a potential target for reducing ALI induced by II/R in the future clinical trial.
肠缺血/再灌注（II/R）诱导的急性肺损伤（ALI）发病率和死亡率较高，其中IL-1β对ALI的充分发展至关重要。然而，这种现象的详细调控机制仍不清楚。本研究的目的是探讨抑制P38丝裂原活化蛋白激酶（MAPK）是否能下调IL-1β的表达，从而保护II/R大鼠的肺免受急性损伤。在此，我们发现与术后8小时（hpo）组和假手术组相比，术后16小时（hpo）肺水肿水平明显升高。免疫荧光染色显示在肺组织中检测到IL-1β和P38 MAPK。与8hpo组和假手术组相比，II/R大鼠在16hpo时肺组织中IL-1β的翻译水平和P38 MAPK的磷酸化水平最高。此外，给予P38α和β的抑制剂SB239063可有效下调IL-1β的表达，并保护II/R大鼠的肺组织免受损伤。我们的研究结果表明，抑制P38α和β可能下调IL-1β的表达，从而保护II/R大鼠的肺免受急性损伤，这可能成为未来临床试验中降低II/R诱导的ALI的潜在靶点。
