中文摘要：

目的评价TNFR-Fc通过下调炎症反应、抑制组织细胞凋亡，对脂多糖（LPS）致急性肺损伤（ALI）小鼠肺组织的保护性作用。方法小鼠随机分为LPS组、TNFRFc＋LPS组和对照组。气管内滴人LPS复制Au小鼠模型，TNFR-Fc＋LPS组在滴入LPS前24h腹膜腔注射TNFR-Fc0．4mg／kg体质量，在滴入LPS后2h收集标本。ELIsA法检测血清肿瘤坏死因子α（TNF-α）及支气管肺泡灌洗液（BALF）中TNF-α、白介素1β（IL-1β）与IL-6浓度，BCA法检测BALF中蛋白含量，qRT-PCR法检测Bax基因转录强度，末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记法检测肺组织细胞凋亡率，组织病理半定量评分评价肺组织损伤程度。结果LPS气管内滴人后，BALF中TNF-α、IL-6浓度与肺泡蛋白含量显著升高（P〈0．05），肺组织Bax基因转录强度均显著增高（P〈0．05），给予TNFRFc预处理显著降低血清TNF-α浓度，BALF中IL-6浓度与蛋白含量也显著下降（P〈0．05），下调Bax基因的转录强度（P〈0．05）。与LPS组相比，TNF融Fc＋LPS组小鼠肺组织细胞凋亡率、病理评分均显著降低（P〈0．05）。结论中和TNF-α能下调肺局部炎症反应强度，减少LPS致ALI小鼠肺组织细胞凋亡，降低LPS气管内滴人引起的肺组织损伤程度。

英文摘要：

Objective Apoptosis has been an important etiological factor of acute lung injury （ALI）. We hypothesized that anti-tumor necrosis factor-α （TNF-α） therapy would have beneficial effects in experimental ALI in mice via apoptosis decreasing. Methods Lipopolysaccharide （LPS） （5 mg/kg） was intratracheally administered to the BALB/c mice （8-10 weeks old）. Before LPS treatment, mice were given TNFR-Fc intraperitoneally once at a dose of 0.4 mg/kg. On 2 hour after LPS treatment, animals were killed. The concentration of TNF-α, interleukin-1β （IL-1β） and IL-6 in serum or BALF were detected by ELISA and protein concentration in BALF were detected. The transcription level of Bax was evaluated by qRT-PCR. The apoptotic cell in ALI mice were detected by TUNEL system. Finally, lung histology was introduced to evaluate lung injury. Results TNFR Fc pretreatment decreased the concentration of TNF-a in serum/BALF and IL-6 in BALF （ P 〈0.05）. TNFR-Fc decreased protein concentration in BALF significantly （P 〈0.05）. ALI mice treated with TNFR-Fc hit a lower transcription level of Bax gene （ P 〈0.05）. TNFR-Fc attenuated lung apoptosis significantly （ P〈0.05）. Lung histology revealed that lung injury induced by LPS was inhibited by TNFR-Fc （ P 〈0.05）. Conclusions Treatment with TNFR Fc significantly attenuates apoptosis and inflammation in LPS- induced ALI mice, meanwhile lung injury improves.