The Prevention Of High Dose Ambroxol In The Ventilaor Induced Lung Injury In Rats

Objective:To explore the effect of the oxidant/antioxidant imbalance in ventilator induced lung injury (VILI) and the prevention of high dose ambroxol, by observing the expression of active protein-1 (AP-1),γ-glutamylcysteine synthetase(γ-GCS) mRNA and protein on different tidal volumes in rats and observing the effect of high dose ambroxol on the expression of AP-1 andγ-GCS in lung of rats in high tidal volume mechanical ventilation.Methods:1 Twenty-four male Wistar rats were divided into three groups randomly: control group, low tidal volume (L-VT) group and high tidal volume (H-VT) group. The levels of MDA in lung and blood were measured by Thiobarbituric acid method. Immunohistochemical staining and molecular hybridization in situ were employed to determine the expression level of AP-1 andγ-GCS mRNA and protein in pulmonary tissues.2 Thirty-two male Wistar rats were divided into four groups:control group, mechanical ventilation group (MV),conventional dose ambroxol pretreatment group (CDAMB) and high dose ambroxol pretreatment group (HDAMB) randomly. The pathologic alterations of the lungs were observed under light microscope in groups;Immunohistochemial staining and molecular hybridization in situ were employed to determine the expression level of AP-1 and y-GCS mRNA and protein in pulmonary tissues.Results:1 Comparing with control group and low tidal volume group, the levels of MDA in lung and blood were highly significant in high tidal volume group (P<0.01); There was no statistics meaning for the differences between low tidal volume group and control group (P>0.05).2 Comparing with control group and low tidal volume group, the expression of AP-1 mRNA and protein were highly significant (P<0.01) in high tidal volume group, with the expression of y-GCS decreased (P<0.01); There was no statistics meaning for the differences between low tidal volume group and control group (P>0.05).3 Apart from the control group,different levels of interstitial and alveolar edema,infiltration and activation of inflammation cells could be seen in experimental groups. There was more obvious pathologic alterations in the MV group.4 The expression of AP-1 mRNA and protein in MV group and CDAMB group are obviously increased compared with control group, and the expression ofγ-GCS was decreased(P<0.01).5 While the expression of AP-1 mRNA and protein in HDAMB group decreased significantly as compared to MV group and CDAMB group, but the expression of y-GCS mRNA and protein increased significantly(P<0.01). But no statistic differences existed between MV group and CDAMB group (P>0.05).Conclusion:1 The over expression of AP-1 mRNA and protein, low expression ofγ-GCS and reduction of GSH can be induced by high tidal volume ventilation, which can lead to the imbalance of oxidant/antioxidant system. It is one of the most important factors in VILI.2 There is small effect on the expression of AP-1 and y-GCS in lung tissue in the L-VT group and no obvious lung injury.3 High dose ambroxol may play a role in the antioxidant therapy of VILI through downregulating the expression of AP-1 mRNA and protein and upregulating y-GCS mRNA and protein.