TNFR-Fc减轻LPS所致小鼠ALI炎症反应损伤

目的: 评价肿瘤坏死因子受体-Fc融合蛋白(TNFR-Fc)能否有效下调炎症反应而减轻急性肺损伤(ALI)小鼠的肺组织破坏。方法: 小鼠随机分为脂多糖(LPS)组、TNFR-Fc+LPS组和对照组。气管内滴入LPS复制ALI小鼠模型,TNFR-Fc组在滴入LPS前24 h腹膜腔注射TNFR-Fc (0.4 mg/kg),在滴入LPS后2 h收集标本,检测肺湿/干重、肺泡蛋白含量与肺组织病理评分;ELISA法检测血清TNF-α浓度及检测肺泡灌洗液与血清IL-1β、IL-6、IL-10与IFN-γ浓度。结果: TNFR-Fc显著降低血清TNF-α浓度(P＜0.05),轻度降低肺湿/干重比例,显著降低BALF蛋白浓度(P＜0.05),显著降低ALI评分数值(P＜0.05)。TNFR-Fc显著降低致炎症细胞因子IL-6在BALF(P＜0.05)与血清(P＜0.05)中的浓度,轻度提高BALF中IL-10浓度(P＞0.05),但其差异不显著,亦能显著提高血清IL-10浓度(P＜0.05)。IL-1β与IFN-γ水平处理前后变化不显著。结论: TNFR-Fc中和ALI中过度表达的TNF-α,下调以IL-6为代表的炎症反应,减轻ALI的肺组织破坏。

Protective role of TNFR-Fc in mouse acute lung injury induced by lipopolysaccharide

AIM: Acute lung injury (ALI) is associated with excessive inflammation caused by high tumor necrosis factor α(TNF-α) concentration. We hypothesized that anti-TNF-α therapy would have beneficial effects on mouse ALI model via down-regulating the inflammation. METHODS: Lipopolysaccharide(LPS,5 mg/kg) was intratracheally administered to BALB/c mice (8~10 weeks old). Twenty-four hours before LPS treatment, the mice were intraperitoneally injected with TNF receptor-Fc fusion protein(TNFR-Fc) once at a dose of 0.4 mg/kg. Wet to dry ratio of the lung tissues and protein concentration in bronchoalveolar lavage fluid(BALF) were detected. The histological changes of the lung tissues were also observed to evaluate lung injury. The concentration of TNF-α in serum as well as interleukin-1β(IL-1β), IL-6, IL-10 and interferon γ(IFN-γ) in BALF and serum were measured by ELISA. RESULTS: TNFR-Fc treatment significantly decreased the concentration of serum TNF-α (P<0.05), the score of the lung histology and protein concentration in BALF (P<0.05). However, the wet to dry ratio of the lung was not obviously changed. The level of IL-6 was decreased both in BALF (P<0.05) and in serum (P<0.05) after TNFR-Fc treatment. The concentration of IL-10 increased significantly in serum (P<0.05) but not in BALF (P>0.05). The concentrations of IL-1β and IFN-γ in BALF and serum were not obviously affected by TNFR-Fc treatment. CONCLUSION: Treatment with TNFR-Fc significantly attenuates LPS-induced ALI via affecting the expression of IL-6 and IL-10.