中文摘要：

目的 探讨肿瘤坏死因子α（ TNF-α） 中和抑制脂多糖（ LPS） 诱导小鼠急性呼吸窘迫综合征（ ARDS） 肺组织细胞凋亡的机制。方法 小鼠随机分为对照组、LPS 组和TNF-α中和组。采用LPS（ 5 mg/kg） 气道雾化造小鼠ARDS 模型, TNF-α中和组在滴入LPS 前24 h 腹腔注射依那西普（ 0. 4 mg/kg） , 滴入LPS 2 h 后收集标本。PCR 检测各组肺组织核转录因子κB（ NF-κB） p65、Bax、Bcl-2的表达水平,Western blot 检测NF-κB p65 和Erk1 /2 及二者磷酸化、Bax、Bcl-2 的蛋白水平; 测量各组肺组织干湿重比; HE 染色观察各组肺组织病理改变, 采用肺损伤半定量评分评估肺组织损伤程度。结果 LPS 组肺组织NF-κB 及Erk1 /2 活化水平升高、Bcl-2 与Bax 比降低（ P 〈0. 05） 。TNF-α中和能明显降低ARDS小鼠肺组织NF-κB 活化水平, Bcl-2 与Bax 比值升高。TNF-α中和组小鼠肺组织湿干重比及肺损伤半定量评分较LPS 组显著降低（ P 〈0. 05） 。结论 TNF-α中和抑制脂多糖诱导小鼠ARDS肺组织损伤, 其机制与抑制Erk1/2、NF-κB 活化, 上调Bcl-2/Bax 比值, 最终减少细胞凋亡密切相关。

英文摘要：

Objective To investigate the mechanism of lung tissue apoptosis in LPS-induced miceARDS via TNF-αneutralization.Methods Thirty-six mice were randomly divided into a control group, aLPS group, and TNF-αneutralization group. LPS（ 5 mg/kg） was intratracheally nebulized to induce ARDS inthe LPS group and the TNF-αneutralization group. Twenty-four hours before LPS treatment, etanercept （ 0.4mg/kg） was abdominal injected to the mice in the TNF-αneutralization group. Mice were sacrificed 2 hoursafter LPS treatment. PCR were used to detected the expression of NF-κB p65, Bax and Bcl-2 in lung tissue.Western blot were used to detected protein level of NF-κB p65, Erk1 /2 and their phosphorylation and Bax,Bcl-2. The lung dry-to-wet ratio was measured. The lung histological changes were evaluated by HE staining.Results Activation level of NF-κB p65 and Erk1 /2 was elevated, the ratio of Bcl-2 and Bax was decreased inthe LPS group（ P 〈 0. 05） . After TNF-αneutralization, the activation level of NF-κB p65 and Erk1 /2 werereduced, the ratio of Bcl-2 and Bax was increased （ P 〈 0. 05） . Compared with the LPS group, the lung dryto-wet ratio and lung injury semi-quantitative score were significantly decreased in the TNF-αneutralizationgroup （ P 〈0. 05） .Conclusion TNF-αneutralization can suppress lung injury in LPS-induced ARDSmiceby inhibiting activation of NF-κB p65 and Erk1/2, increasing the ratio of Bcl-2 and Bax ratio, and eventuallyreducing apoptosis.