| ObjectiveTo investigate the role of TNF-αand the influence of recombinant human tumor necrosis factor-Fc on pathogenesis of chronic obstructive pulmonary disease of rats.MethodsForty eight rats were randomly divided into a normal control group, a COPD group, a rhTNFR: Fc-interfered group and a sham interfered group. Rat models of COPD were established by exposure to cigarette smoking daily for 80 days. rhTNFR: Fc-interfered group was interfered with rhTNFR: Fc, the sham interfered group injected with certain praeparatum as control for rhTNFR: Fc-interfered group. Lung function was detected in half rats of every group, the levels of Tumor necrosis factor alpha(TNF-α)in serum and BALF measured with ELISA. Total cell counts, neutrophil counts and neutrophil proportion in BALF were examined. Lung tissure section stained by hematoxylin and eosin (HE) was observed to study the morphological alternations. Mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods were carried out to examined the percentage of positive cells and distribution of apoptotic cells. The concentration of VEGF in BALF was examined with ELISA, the expression of VEGFR-2 and MMP-9 measured by Western blot and levels of albulmin in serum measured by automatic biochemistry analyzer.ResultsCompared with the normal control and rhTNFR: Fc-interfered group, FEV0.3/FVC and PEF were lower in COPD rats (P＜0.05); Compared with rhTNFR: Fc-interfered group, FEV0.3/FVC and PEF were lower in sham interfered group(P＜0.05). The levels of TNF-αin serum were higher in COPD group than in the normal control (P＜0.05) and rhTNFR: Fc-interfered group (P＜0.05). Significanct differences were found between the levels of TNF-αin serum of rhTNFR: Fc-interfered group and sham interfered group(P＜0.05). The levels of TNF-αin BALF were higher in COPD group than in the normal control(P＜0.05), but no significanct differences were found between the levels in COPD group and rhTNFR: Fc-interfered group. Total cell counts and neutrophil counts and neutrophil proportion in BALF were higher in COPD group than in the normal control and rhTNFR: Fc-interfered group (P＜0.01, p＜0.05), and they were also higher in rhTNFR: Fc-interfered group than in sham interfered group (P＜0.01, p＜0.05). MLI in COPD rats was higher than that in the normal control(p＜0.05) while MAN was decreased on the contrary(p＜0.05), compared with normal control and rhTNFR: Fc-interfered group. Significanct differences were found between MAN in rhTNFR: Fc-interfered group and sham interfered group. The number of TUNEL＋cells in alveolar septa was significantly increased in COPD group as compared with normal control and rhTNFR: Fc-interfered group(P＜0.05), so was it in the latter compared with sham interfered group.The concentration of VEGF in BALF of COPD group was significantly decreased as compared with normal control group, but no significanct differences were found between the concentration of COPD group and rhTNFR: Fc-interfered group (p＞0.05). The expression of VEGFR-2 protein in COPD group was significantly decreased compared with normal control group while no differences existed between that in COPD group and rhTNFR: Fc-interfered group (p＞0.05). The expression of MMP-9 was decreased in rhTNFR: Fc-interfered group compared with COPD group(P＜0.05).The weight of COPD group was significantly decreased compared with normal control group and rhTNFR: Fc-interfered group (p＜0.01). No differences were found between the weight of COPD group and the control group for interfered one (p＞0.05), significant differences found between the weight of rhTNFR: Fc-interfered group and control group for interfered one (p＜0.01 ). The levels of albulmin in serum of COPD group were significantly decreased compared with normal control group (p＜0.05), but no differences were found among the levels of COPD group and rhTNFR: Fc-interfered group and control group for interfered one (p＞0.05). Negative correlations were demonstrated between the levels of TNF-αin serum and BALF of (COPD group＋sham interfered group) and PEF and FEV0.3/FVC(p＜0.05). The levels of TNF-αin serum of COPD group revealed negative correlations to the weight (r=-0.75, p＜0.05) and the levels of serum albumin (r=-0.73, p＜0.05).ConclusionsTNF-αrelates to the pathogenesis of COPD of smoking rats and causes pulmonary pathological changes, airway inflammation, decline of pulmonary function, apoptosis of alveolar septal cells and malnutrition in smoking rats. Decrease of VEGF and VEGFR may contribute to the pathogenesis of emphysema of smoking rats. rhTNFR: Fc may play certain role in the improvement of pulmonary pathological changes, reduction of airway inflammation, decrease of alveolar septal apoptosis, slowdown of pulmonary function impairment of COPD and improvement of nutritional status.
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