硫化氢对脂多糖诱导急性肺损伤的保护作用

摘要

目的 探讨硫化氢对急性肺损伤(acute lung injury,ALI)的保护作用及其机制.方法 雄性SD大鼠共48只,随机分为脂多糖组(n=24)和脂多糖+NaHS组(n=24).3 h后检测肺组织髓过氧化物酶(MPO)活性、丙二醛(MDA)含量、核转录因子-κB(NF-κB)活性、Toll 样受体(Toll like receptor,TLR) 4 mRNA、巨噬细胞移动抑制因子 (macrophage migration inhibitory factor,MIF)mRNA、肺湿质量/干质量(W/D)、肺组织的病理变化和外周血中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量.结果 脂多糖+NaHS组肺损伤显著改善.与脂多糖组比较,脂多糖+NaHS组肺组织TLR4和MIF mRNA 表达降低,MPO活性、MDA含量、肺W/D下降,血浆TNF-α、IL-6含量降低.结论硫化氢可通过抑制TLR4和MIF的表达减轻ALI的肺部炎性反应.%Objective To study protective effect of hydrogen sulfide ( H2 S) against acute lung injury and its underlying mechanisms. Methods Fourty - eight Sprague - Dawley rats were randomly divided into lipopolysaccharide ( LPS) group and LPS + NaHS group, with 24 rats in each. After 3 hours, myeloperoxidase (MPO) activity, malondialdehyde (MDA) , nuclear factor - KB ( NF - KB) activity, toll - like receptors ( TLR) 4 mRNA, macrophage migration inhibitory factor ( MIF) mRNA, the wet - to - dry weight ( W/D) ratio, and histological changes of the lung tissue were measured. Blood sample was collected to analysis tumor necrosis factor - α ( TNF - α ) and interleukin - 6 ( IL - 6 ) . Results LPS + NaHS significantly improved the lipopolysaccharide - induced histological changes. TLR 4 mRNA, MIF mRNA, MPO, NF - KB activity, MDA, and W/D ratio of lung tissue were significantly lower in the LPS + NaHS group than those in the LPS group ( P < 0. 05 ) . Serum level of TNF - α and IL - 6 were also significantly lower in the LPS + NaHS group ( P < 0. 05 ) . Conclusion These results suggest that H2S protects against acute lung injury by inhibiting TLR4 and MIF.