Effects of high dose ambroxol on expression of active protein-1 and γ-glutamylcysteine synthetase in lung of rats with mechanical ventilation

Abstract

Objective To explore the role of high dose ambroxol in ventilator induced lung injury (VILI)by investigating the effect of different dose ambroxol on expression of active protein-1(AP-1)and γ-glutamylcysteine synthetase(γ-GCS)in lung of rats with mechanical ventilation(MV).Methods Thirty-two male Wistar rats were randomly divided into four groups: control group,MV group, conventional dose ambroxol pretreatment group(CDAMB)and high dose ambroxol pretreatment group (HDAMB).The Mrna and protein expressions of AP-1 and γ-GCS in lung tissues were determined by immunohistochemical staining and molecular hybridization in situ.Results The Mrna and protein expressions of AP-1 in MV group and CDAMB group were obviously higher than those of control group,and the Mrna and protein expressions of γ-GCS in MV group and CDAMB group were obviously lower than those of control group(P <0.01).The Mrna and protein expressions of AP-1 in HDAMB group were obviously lower than those of MV group and CDAMB group,and the Mrna and protein expressions of γ-GCS were higher than those of MV group and CDAMB group(P <0.01).There was no statistical difference in each index between MV group and CDAMB group.Conclusions The oxidation/antioxidation imbalance is involved in the pathogenesis of VILI.High dose ambroxol may play a role in the antioxidant therapy of VILI through downregulating AP-1 expression and upregulating γ-GCS expression. Key words: Mechanical ventilation; Active protein-1; γ-glutamylcysteine synthetase; Ambroxol