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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~(-6)m/个]显著高于正常对照组[(44±7)×10~(-6)m/个],其平均肺泡数[(252±97)×10~6个/m~2]显著低于正常对照组[(393±24)×10~6个/m~2]和干预组[(379±33)×10~6个/m~2]。假干预组平均肺泡数[(213±99)×10~6个/m~2]显著低于干预组[(379±33)×10~6个/m~2]。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。
Objective To investigate the effect of recombinant human Tumor Necrosis Factor Receptor - Antibody Fusion Protein (rhTNFR) on lung function in rats with chronic obstructive pulmonary disease (COPD). Methods Forty eight rats were randomly divided into normal control group, COPD group, rhTNFR: Fc intervention group (intervention group) and sham intervention group. The model of COPD was established by the simple smoking method. The intervention group received rhTNFR: Fc subcutaneously for intervention, and the sham intervention group received subcutaneous injection of blank simulant. The levels of tumor necrosis factor alpha (TNF-α) in serum and bronchoalveolar lavage fluid (BALF) of each group were measured by enzyme-linked immunosorbent assay (ELISA). Lung tissue sections were stained with hematoxylin-eosin to observe the morphological changes. The average lung lining interval and the average alveolar number were quantitatively determined, and lung function was determined by the small animal lung function measuring system. Results The forced expiratory volume occupancy capacity (FEV 0.3 / FVC) and peak expiratory flow (PEF) [(65.1 ± 8.4)% vs (18.8 ± 1.6) ml / s] in COPD group were significantly lower than those of normal (85.6 ± 5.9)% and (47.2 ± 7.3) ml / s in the control group and (77.7 ± 2.7)% and (38.2 ± 3.3) ml / s in the intervention group and FEV0.3 / FVC and PEF [(65.4 ± 9.8)% and (19.0 ± 1.9) ml / s] was significantly lower than the intervention group. The serum level of TNF-α in COPD group [(118 ± 34) ng / L] was significantly higher than that in normal group [(74 ± 16) ng / L) and [79 ± 14] ng / L in intervention group The concentration of TNF-α in serum [(120 ± 39) ng / L] was significantly higher than that in the intervention group; the concentration of TNF-α in BALF of COPD group was significantly higher than that of the control group [(79 ± 28) ng / L 28) ng / L]. The average interval of lung lining in COPD group was significantly higher than that in control group [(77 ± 29) × 10 ~ (-6) m / s) [(44 ± 7) × 10 ~ (-6) m / The number of alveoli was significantly lower than that in the control group [(252 ± 97) × 10 ~ 6 / m ~ 2] [(393 ± 24) × 10 ~ 6 / m ~ 2] and [379 ± 33 × 10 ~ 6 / m ~ 2]. The average number of alveoli in the sham group [(213 ± 99) × 10 ~ 6 / m ~ 2] was significantly lower than that in the intervention group [(379 ± 33) × 10 ~ 6 / m ~ 2] The concentrations of TNF-α in serum and BALF of COPD group + sham group were negatively correlated with both PEF and FEV_ (0.3) / FVC. Conclusion TNF-α is associated with COPD in smoking rats and affects its pulmonary function. RhTNFR: Fc may play a role in retarding pulmonary function impairment.