急性肺损伤的炎症反应机制与药物治疗探讨

Effects of tripterygium wilfordii hood T4 on lipopolysaccharideinduced acute lung injury in mice

目的：探讨急性肺损伤的炎症反应机制以及雷公藤单体Ｔ４（Ｔ４）对炎症反应的影响。方法：小鼠腹腔注射内毒素（ＬＰＳ）复制急性肺损伤模型。动物分为生理盐水对照组、ＬＰＳ组、Ｔ４组（腹腔注射Ｔ４ ８５ μｇ／ｋｇ）和地塞米松组（地塞米松７０ ｍ ｇ／ｋｇ）。酶联免疫吸附法测定肿瘤坏死因子 α（ＴＮＦ α）、白细胞介素 １β（ＩＬ １β）、ＩＬ ６ 和ＩＬ １０ 浓度。一氧化氮（ＮＯ）的产物ＮＯ－２ 浓度以Ｇｒｉｅｓｓ法测定。以肺湿重与干重比值反映肺含水量。结果：Ｔ４组小鼠肺湿重与干重比值（３．９０±０．６２）与ＬＰＳ组（５．９５±０．９９）比较显著降低（Ｐ＜ ０．０５）。ＬＰＳ组血浆ＴＮＦ α、ＩＬ １β和ＩＬ ６浓度分别为（１３２．５±５．０）ｎｇ／Ｌ、（１８３．７±５８．６）ｎｇ／Ｌ和（３ ２９０．１±９２４．２）ｎｇ／Ｌ，Ｔ４组血浆ＴＮＦ α（０ ｎｇ／Ｌ）与ＬＰＳ组比较显著降低，Ｔ４ 组血浆ＩＬ １β和ＩＬ ６〔（３９．１±３１．８）ｎｇ／Ｌ和（８５９．６±８２９．９）ｎｇ／Ｌ〕与ＬＰＳ组比较亦显著降低。与ＬＰＳ组比较，Ｔ４ 组小鼠肺泡灌洗液中ＴＮＦ α浓度从（２２９．３±２０．３）ｎｇ／Ｌ显著降低到（２８．５±３３．４）ｎｇ／Ｌ。

Objective:To observe the effects of tripterygium wilfordii hood T4 (T4) and dexamethasone on proinflammatory and antiinflammatory response in lipopolysaccharide (LPS)induced acute lung injury.Methods:Mice were divided into saline controls,LPS group,T4 group (85 μg/kg),and dexamethasone group (70 mg/kg).Tumor necrosis factorα (TNFα),interleukin1β(IL1β),IL6 and IL10 were measured by ELISA.The pulmonary extravascular lung water was determined by lung wet to dry weight ratio.Results:There was a significant increase in pulmonary extravascular lung water in LPS group compared to T4 group (5 95±0 99 vs.3 96±0 52, P <0 05).Plasma levels of TNFα,IL1β,IL6 were increased in LPS group 〔(132 5±5 0)ng/L,(183 7±58 6)ng/L,and (3 290 1±924 2)ng/L,respectively〕,however,they were markedly decreased by the treatment with T4 〔0 ng/L,(39 1±31 8)ng/L,and (859 6±829 9)ng/L,respectively〕.Moreover,TNFα levels in alveolar lavage were also significantly lower in T4 group than that in LPS group 〔(28 5±33 4)ng/L vs.(229 3±20 3)ng/L〕.As compared with LPS gorup,the lung wet to dry ratio decreased markedly in dexamethasone and T4 groups.Conclusions