抑制一氧化氮合成对急性肺损伤炎症反应的调节作用

Effects of nitric oxide inhibition on inflammatory response in acute lung injury

目的 :研究抑制一氧化氮对脂多糖 (LPS)诱导肺损伤炎症反应的影响。方法 :ELISA检测TNFα、IL 1β、IL 6和IL 10浓度 ,Griess法测定亚硝酸盐浓度。肺湿干重比反映小鼠肺损伤程度。结果 :小鼠腹腔注射LPS 2 0mg/kg后 ,血浆及肺泡灌洗液 (BALF)中TNFα、IL 1β、IL 6、IL 10和亚硝酸盐浓度显著升高。LPS注射前 30min给予地塞米松 70mg/kg,血浆TNFα、IL 1β、IL 6、IL 10及亚硝酸盐浓度明显降低 ,而BALF中IL 1β、IL 6、IL 10浓度明显降低。给予一氧化氮合酶抑制剂S 硫酸甲基异硫脲 (SMT) 85mg/kg ,血浆IL 1β和IL 6明显升高 ,BALF中TNFα明显升高 ,而IL 1β、IL 6和IL 10无明显改变。与LPS组相比 ,地塞米松组肺湿干重比明显降低 ,而SMT组相反。结论 :抑制一氧化氮引起促炎性细胞因子释放增加 ,并加重肺损伤。

Aim:To observe the effects of nitric oxide inhibition on inflammatory reaction by lipopolysaccharides(LPS) induced lung injury.Methods:The levels of tumor necrosis factor α(TNFα),interleukin 1β(IL 1β),IL 6,and IL 10 in mouse bronchoalveolar lavage fluid(BALF)and plasma were measured by ELISA.Nitrite was measured by Griess reaction.In animal model,the degree of LPS induced acute lung injury was evaluated by the wet and dryweight ratio of lung.Results:The levels of TNFα,IL 1β,IL 6,IL 10 and nitrite in mice plasma and BALF after LPS 20 mg/kg ip increased markedly at 12 h.Dexamethasone(Dex)70mg/kg injected ip at 30 min before ip LPS decreased the concentrations of TNFα,IL 1β,IL 6,IL 10,and nitrite in plasma.But IL 1β,IL 6,and IL 10 decreased in BALF.S methylisothiourea sulfate(SMT),a nitric oxide synthetase inhibitor,85mg/kg injected ip at 30 min before LPS increased the levels of IL 1β,and IL 6 in plasma.In BALE,TNFα increased,whereas IL 1β,IL 6,and IL 10 remained unchanged.Compared to LPS group,the wet and dry lung weight ratio decreased significantly in Dex group,but the ratio increased in SMT group.Conclusion:Inhibition of nitric oxide may result an enhanced production of proinflammatory cytokines and an increased LPS induced lung injury.