外源性硫化氢在脂多糖致老年大鼠急性肺损伤中的作用

Roles of exogenous hydrogen sulfide in acute lung injury induced by lipopolysaccharide in aged rats

目的:探讨外源性硫化氢(H2S)在脂多糖(LPS)致老年大鼠急性肺损伤(ALI)中的作用并初探其机制。方法:将48只SD老年大鼠随机分为对照组、LPS组(经气管内滴注LPS复制ALI模型)和NaHS+LPS组(LPS滴注前10min腹腔注射NaHS),每组16只。分别于给药后4及8h取8只动物处死,测定肺系数;光镜下观察肺组织形态学改变;检测血浆H2S、NO和CO含量,肺组织丙二醛(MDA)含量,胱硫醚-γ-裂解酶(CSE)、诱导型一氧化氮合酶(iNOS)和血红素加氧酶(HO)活性;用免疫组织化学法检测肺组织iNOS及HO-1蛋白的表达。结果:给药后4及8h,LPS组肺系数及IQA大于对照组和NaHS+LPS组,NaHS+LPS组大于对照组(P均<0.001)。与对照组比较,LPS组肺组织MDA含量增加;血浆H2S含量和肺组织CSE活性下降;肺组织iNOS活性和iNOS蛋白表达增强,血浆NO含量增加;肺组织HO活性和HO-1蛋白表达增强,血浆CO含量增加(P均<0.05)。与LPS组比较,NaHS+LPS组上述指标均有所改善(P均<0.01)。结论:CSE/H2S体系的下调是LPS致老年大鼠ALI发病的机制之一,外源性H2S可通过抗氧化和下调iNOS/NO体系、上调HO-1/CO体系对肺组织发挥保护作用。

Aim：To explore the role of exogenous hydrogen sulfide（H2S） in lipopolysaccharide（LPS）-induced acute lung injury（ALI） in aged rats.Methods：Fourty-eight SD aged rats were randomized into three groups：control group,LPS group（instilled with LPS intratracheally to induce ALI）,and NaHS＋LPS group（injected NaHS abdominally before LPS instillation）,and 16 in each group. Animals were sacrificed at 4 and 8 h after agent administration. Lung weight/body weight ratio（LW/BW） was calculated. Morphological changes of lung tissue were observed. The plasma levels of H2S,NO and CO were tested. Malondialdehyde（MDA） content,cystathionine-γ-lyase（CSE）,inducible nitric oxide synthase（iNOS） and hemeoxygenase（HO） activity in lung tissue were determined. Immunohistochemistry technique was performed to examine the expression of iNOS and HO-1 protein in lung tissue.Results：Compared with those of the control group,IQA,LW/BW and MDA content in lung tissue of the LPS group were higher,the plasma levels of H2S and CSE activity in lung tissue were lower,the activity of iNOS and HO,the protein expression of them in lung tissue were higher,and the levels of NO and CO in plasma were higher（P0.05）.The indexes mentioned above in NaHS＋LPS group were improved compared with those in LPS group（P0.05）.Conclusion：Downregulation of CSE/H2S is involved in the pathogenesis of ALI induced by LPS. Exogenous H2S may provide protection against the lung injuries to some extent,which may be explained by its anti-oxidative effects,the downregulation iNOS/NO system and the upregulation of HO-1/CO system.