硫酸甲基异硫脲对急性肺损伤小鼠肺组织核因子-κΒ活性的影响

Effect of S-methylisothiourea sulfate on pulmonary nuclear factor-κΒ in mice with acute lung injury

目的 探讨硫酸甲基异硫脲 (SMT)对急性肺损伤小鼠肺组织核因子 (NF) κΒ活性的影响。方法 利用腹腔内注射内毒素 (LPS)诱导小鼠急性肺损伤模型 ,180只小鼠随机分为LPS组、LPS +SMT组 (LPS注射前腹腔内注射SMT2 0mg/kg) ,LPS注射后 0h、1h、3h、6h、12h迁移率改变电泳法 (EMSA)检测肺组织NF κΒ活性 ,同时测定肺组织中肿瘤坏死因子 (TNF)α、白介素 10 (IL 10 )浓度及其mRNA表达 ,并观察肺组织的病理改变。结果 与LPS组比较 ,1～ 12hSMT组肺组织核蛋白NF κΒ活性明显增强 (P <0 0 5 ) ;肺组织匀浆细胞因子TNFα及其mRNA表达显著增高(P <0 0 5 )。与LPS组比较 ,SMT组IL 10及其mRNA表达均明显下降。结论 SMT通过活化NF κΒ ,启动炎症因子表达 ,但同时抑制抗炎介质的表达 。

Objective To investigate the effect of S methylisothiourea sulfate(SMT)on pulmonary nuclear factor(NF) κΒ in mice with acute lung injury(ALI)induced by lipopolysaccharide(LPS).Methods All mice were randomly allocated to two groups(LPS,LPS+SMT group).SMT(20 mg/kg)was injected intraperitoneally 30min before LPS injection.At 0h,1h,3h,6h and 12h after LPS exposure,the total lung homogenates were prepared to detect NF κΒ activity by EMSA,tumor necrosis factor (TNF)α and interleukin IL 10 levels by ELISA and their mRNA expression by RT PCR.Meanwhile,pathologic changes were examined.Results As compared with LPS group,NF κΒ activity in lung homogenates elevated at 1 h and raised markedly until 12 h in SMT group( P< 0 05).At 3 h to 12 h,TNFα level and mRNA expression in SMT group increased obviously ( P< 0 05).Compared with LPS group,IL 10 level and mRNA expression decreased significantly in SMT group.Conclusion SMT resulted in NF κΒ activation,and leaded to severe lung injury.