AUTHOR=Wang Tiantian , Liu Chunxia , Pan Ling-hui , Liu Zhen , Li Chang-long , Lin Jin-yuan , He Yi , Xiao Jing-yuan , Wu Siyi , Qin Yi , Li Zhao , Lin Fei 

TITLE=Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood–Air Barrier Hyperpermeability

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.569251

DOI=10.3389/fphar.2020.569251

ISSN=1663-9812

ABSTRACT=Lung ischemia-reperfusion injury (LIRI) is a complex pathophysiological process during many clinical conditions, such as lung transplantation, acute lung injury (ALI), etc. The function of p38 Mitogen-activated protein kinase (MAPK) in LIRI is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI and explored the mechanism of inhibiting p38 MAPK in pulmonary blood-air hyperpermeability both in vivo and vitro. 72 rats were divided into four groups at random: Control group, I/R (ischemia-reperfusion) group, SB203580 (p38 MAPK inhibitor) group and I/R+SB203580 group. The rat pulmonary microvascular endothelial cells (rPMVECs) were divided into five groups: control group, control shRNA group, p38 MAPK shRNA group, OGD/R group (cells subjected with non-serum and -glucose medium for 1 h, followed by reoxygenation for 4 h) and OGD/R+p38 MAPK shRNA group. Degree of lung injury was assessed by HE staining, TEM and inflammatory response. Pulmonary blood-air barrier permeability was evaluated by evans blue, W/D ratios and total proteins in BALF. Protein expression of AQP1, ICAM-1, ZO-1 and VE-cadherin were estimated by western blot and Immunohistochemistry in vivo and vitro I/R model. Lung I/R induced lung injury and high permeability of blood-air barrier while pretreatment with SB203580 decreased lung injury and reduced the high permeability of blood-air barrier in rat models. In vitro rPMVECs model, OGD/R promoted hyperpermeability of endothelial barrier. However, inhibition of p38 MAPK attenuated OGD/R-induced cell injury and thus maintained endothelial barrier integrity. Summarily, our results proved that inhibition of p38 MAPK alleviates LIRI through decreasing pulmonary inflammation and blood-air hyperpermeability.