Role of hydrogen sulfide in acute lung injury induced by lipopolysaccharide in rats / 基础医学与临床

ABSTRACT

Objectives To explore the role of hydrogen sulfide(H_(2)S) in lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and the underlying mechanisms.Methods Sixty-four Sprague-Dawley rats were randomly divided into four groups control,LPS(instilled intratracheally to induce ALI),NaHS(H_(2)S donor)+LPS,propargylglycine [inhibitor of cystathionine-?-lyase(CSE),PPG]+LPS.Animals were sacrificed at(4 h) or 8h after agent administration.Lung weight/body weight ratio(LW/BW) was measured and calculated.Morphological changes of lung tissues were observed,H_(2)S concentration and carbon monoxide(CO) level in plasma were tested.Malondialdehyde(MDA) content,CSE activity and heme oxygenase(HO) activity of the lung were determined.Immunohistochemisty technique was performed to examine the expression and the absorbance value of(HO1) protein in lung tissues.Results Compared with control conditions,severe injuries of lung tissues and a raised LW/BW and MDA content were observed in rats treated with LPS.LPS also lead to a drop in plasma H_(2)S concentration and lung CSE activity.The enzyme activity of HO,the protein expression of(HO-1) and plasma CO level increased after LPS instillation. Administration of NaHS before LPS could atten-uated the changes induced by LPS.Pre-administration of PPG exacerbated the injuries induced by LPS,but there was no prominent variation in CO level,HO activity and(HO-1) protein expression compared with those of LPS group.Conclusions Downregulation of H_(2)S/CSE was involved in the pathogenesis of acute lung injury induced by LPS.Exogenous(H_(2)S) provided protection against the lung injuries to some extent,which may be explained by its anti-oxidative effects and the upregulation of CO/(HO-1) system.