【摘要】 目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rhTNFR:Fc）对大鼠慢性阻塞性肺疾病（COPD）模型肺功能的影响。方法 48只大鼠随机分为正常对照组、COPD 组、rhTNFR:Fc 干预组（简称干预组）及假干预组。单纯吸烟法建立 COPD 模型,干预组皮下注射 rhTNFR:Fc 进行干预,假干预组皮下注射空白模拟制剂。酶联免疫吸附法（ELISA）测定各组血清和支气管肺泡灌洗液（BALF）中的肿瘤坏死因子α（TNF-α）浓度。肺组织切片行苏木精-伊红染色观察形态学改变,定量测定肺平均内衬间隔和平均肺泡数,用小动物肺功能仪测定系统测定肺功能。结果 COPD 组0.3秒用力呼气容积占用力肺活量比值(FEV_0.3/FVC)和呼气峰流速（PEF）[（65.1±8.4）%和（18.8±1.6）ml/s]显著低于正常对照组[（85.6±5.9）%和（47.2±7.3）ml/s]和干预组[（77.7±2.7）%和（38.2±3.3）ml/s],假干预组 FEV_0.3/FVC 和 PEF[（65.4±9.8）%和（19.0±1.9）ml/s]显著低于干预组。COPD 组血清中TNF-α浓度[（118±34）ng/L]显著高于正常组[（74±16）ng/L]和干预组[（79±14）ng/L],假干预组血清中 TNF-α浓度[（120±39）ng/L]显著高于干预组;COPD 组 BALF 中TNF-α浓度[（155±28）ng/L]显著高于正常对照组[（79±28）ng/L]。COPD 组肺平均内衬间隔[（77±29）×10^-6m/个]显著高于正常对照组[（44±7）×10^-6m/个],其平均肺泡数[（252±97）×10⁶个/m²]显著低于正常对照组[（393±24）×10⁶个/m²]和干预组[（379±33）×10⁶个/m²]。假干预组平均肺泡数[（213±99）×10⁶个/m²]显著低于干预组[（379±33）×10⁶个/m²]。COPD 组+假干预组血清和 BALF 中 TNF-α浓度与 PEF 和 FEV_0.3/FVC 均呈显著负相关。结论 TNF-α与吸烟大鼠的 COPD 形成有关,并影响其肺功能;rhTNFR:Fc 对延缓肺功能损害具有一定的作用。更多还原

【Abstract】 Objective To investigate the influence of recombinant human tumor necrosis factor-Fc （rhTNFR:Fc）on pulmonary function in a rat model of chronic obstructive pulmonary disease（COPD）. Methods Forty-eight rats were randomly divided into a normal control group,a COPD group,a rhTNFR: Fc-intervention group and a sham intervention group.The COPD model was established by exposure to cigarette smoking daily for 80 days.The intervention group was treated with rhTNFR:Fc,and the sham intervention group injected with a preparation（normal saline 0.1 ml,manicol 0.8 ml,cane sugar 0.2 mg, Tris 0.024 mg）as control.The levels of tumor necrosis factor alpha（TNF-α）in serum and BALF were measured with ELISA.Lung tissue section stained by hematoxylin and eosin was observed to study the morphological alternations.Mean linear intercept（MLI）and mean alveolar numbers（MAN）were measured,and the lung function detected.Results Compared with the normal control[（85.6±5.9）%, （47.2±7.3）ml/s],and the rhTNFR:Fc-intervention group[（77.7±2.7）%,（38.2±3.3）ml/s], FEV_0.3/FVC and PEF were lower in the COPD rats[（65.1±8.4）%,（18.8±1.6）ml/s].The levels of TNF-α in serum were higher in the COPD group[（118±34）ng/L]than in the normal control[（74±16） ng/L]and the rhTNFR:Fc-intervention group[（79±14）ng/L].Significant differences were found between rhTNFR:Fc-intervention group and sham intervention group.The levels of TNF-α in BALF were higher in the COPD group[（155±28）ng/L]than in the normal control[（79±28）ng/L],but no significant differences were found between the levels in the COPD group and the sham intervention group. MLI in the COPD rats[（77±29）×10^-6m]was higher than that in the normal control[（44±7）×10^-6m] while MAN was decreased on the contrary,compared with the normal control and the rhTNFR:Fc- intervention group.Significant differences were found between MAN in the rhTNFR:Fc-intervention group and the sham intervention group.Negative correlations were demonstrated between the levels of TNF-α in serum and BALF and PEF and FEV_0.3/FVC in the COPD group + sham intervention group.Conclusions TNF-α contributes to the pathogenesis of COPD and affects pulmonary function,rhTNFR:Fc may play a role in the improvement of pulmonary function in COPD.更多还原