The effects of mitogen-activated protein kinases on the genes expression of the pulmonary surfactants from alveolar epithelial cells during ventilation induced lung injury in rats

Abstract

Objective To investigate the effects of mitogen-activated protein kinases (MAPK) on the genes expression of the pulmonary surfactants from alveolar epithelial cells during ventilation induced lung injury in rats.Methods Anesthetized male SD rats were randomized into six groups:① Control group(C) received no mechanical ventilation.② Low-volume ventilation(LV) group received mechanical ventilation with Vt=6 ml/kg,RR=40 bmp,I∶E=1∶2,FiO2=21％,positive end-expiratory pressure =0.③ Hyperventilation(HV) group received mechanical ventilation with the same respiratory parameters as the LV group and the Vt was 40 ml/kg.The inhibitors of MAPK including the JNK's:SP600125,the ERK's:PD98059 and the p38's:SB203580 were pretreated 30 min before ventilation just like in the HV group.④ SP600125 group (SP600125 + HV group).⑤ PD98059 group (PD98059 + HV group).⑥ SB203580 group (SB203580 + HV group).After 4 h ventilation,the animals in each group were killed and the lungs were removed for detecting the expression of SP-A,B,C and RTI40 mRNA by RT-PCR.Results ① Compared with group C,the expression of RTI40 mRNA of lung tissue increased significantly in the LV group and the HV group (P＜0.05),but the expression of SP-A,SP-C mRNA decreased in the HV group,SP600125 group and SB203580 group (P＜0.05),while there was no significant difference in the expression of SP-A、C mRNA in LV groups and PD98059 group (P＜0.05).② Compared with the HV group,the SP-A,C gene expressions of lung tissue in SP600125 group,PD98059 group and SB203580 group increased significantly (P＜0.05),but RTI40 gene expressions decreased(P＜0.05).③ The SP-A,C gene expressions of lung tissue in PD98059 group increased significantly than those of SP600125 group and SB203580 group.④ The SP-B gene expression had no difference in all groups.Conclusions The results of our study show that mechanical ventilation inhibited the expressions of the SP-A and SP-C,but upregulated RTI40 gene expressions.The inhibitors of MAPK attenuated the changes of SP-A,C and RTI40 mRNA during the process of high volume ventilation,which indicates that MAPK,at least in part,may play a role in the functions of Ⅰ and Ⅱ alveolar epithelial cells in the lung injury induced by mechanical ventilation. Key words: Ventilation induced lung injury; Pulmonary surfactant; Genes expression; Mitogen-activated protein kinases