Role of p38 mitogen activated protein kinase signaling pathway in lung ischemia-reperfusion protection offered by HOE642 / 中南大学学报(医学版)

ABSTRACT

Objective:To explore the protective effect of sodium channels antagonists HOE642 on lung ischemia reperfusion and the role of the p38 mitogen activated protein kinase (p38MAPK) signaling pathway in this process.Methods:A total of 36 mice were randomly divided into a sham operation group (SHAM group),a lung ischemia reperfusion group (I/R group) and a lung ischemia reperfusion+HOE642 group (HOE group).The water content was detected by electronic scales,and the lung tissue pathological changes were observed under optical microscope.The inflammatory cytokines including IL-6 and TNF-α were examined by ELISA.The intracellular calcium fluorescence intensity was examined and observed under fluorescence microscope,and the protein expression of p38MAPK was detected by Western blot.Results:Lung water content in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P＜0.05).Lung interstitial edema,hemorrhage,lung tissue inflammatory cells infiltration were significantly alleviated in the HOE group than those in the I/R group,while the injury in the HOE group was aggravated than those in the SHAM group (both P＜0.05).T he IL-6 and TNF-α in lung tissues in the HOE group were lower than those in the I/R group,but higher than those in the SHAM group (both P＜0.05).Intracellular calcium fluorescence intensity in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P＜0.05).The protein expression of p38MAPK in lung tissues in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P＜0.05).Conclusion:HOE642 may exert protective effect on pulmonary I/R injury through regulation of the p38MAPK signaling pathway,resulting in reduction of intracellular calcium ion concentration and calcium overload,and decrease of inflammatory response.