硫化氢在脂多糖所致大鼠急性肺损伤中的作用

Role of hydrogen sulfide in acute lung injury induced by lipopolysaccharide in rats

目的探讨硫化氢(H2S)在脂多糖(LPS)所致大鼠急性肺损伤(ALI)中的作用及可能的机制。方法将64只SD大鼠随机分为对照组、LPS组(经气管内滴注LPS复制ALI)、NaHS+LPS组和炔丙基甘氨酸(PPG)+LPS组。给药后4 h或8 h处死,测定肺系数;光镜观察肺组织形态学改变;化学法检测血浆H2S和CO含量、肺组织丙二醛(MDA)含量、胱硫醚-γ-裂解酶(CSE)和血红素加氧酶(HO)活性;用免疫组织化学法检测肺组织HO-1蛋白表达及吸光度值。结果气管内滴注LPS可引起肺组织明显的形态学改变;肺系数和肺组织MDA含量增加;血浆H2S含量和肺组织CSE活性下降;肺组织HO活性和HO-1蛋白表达增强;血浆CO含量增加。预先给予NaHS可显著减轻LPS所致上述指标的改变。而预先给予PPG可加重LPS所致肺损伤,但对CO含量、HO活性和HO-1蛋白表达无明显影响。结论H2S/CSE体系的下调在LPS所致ALI的发病学中有一定作用,而外源性给予一定量的NaHS对肺组织具有保护作用,该作用可能与其抗氧化效应和上调CO/HO-1体系有一定关系。

Objectives To explore the role of hydrogen sulfide （H2S） in lipopolysaccharide （LPS）-induced acute lung injury （ALl） 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）, Nails （ H2S donor） ＋ LPS, propargylglycine[ inhibitor of cystathionine-γ-lyase （CSE）, PIG] ＋ 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, H2S 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 HO-1 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 L PS. LPS also lead to a drop in plasma H2S 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 NailS before LPS could attenated 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. Conclusioons Downregulation of H2S/CSE was involved in the pathogenesis of acute lung injury induced by LPS. Exogenous H2S 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 .