慢性阻塞性肺疾病大鼠模型肿瘤坏死因子α及受体的表达及意义

目的探讨肿瘤坏死因子α（TNF—α）与肿瘤坏死因子受体1（TNFR1）在慢性阻塞性肺疾病（COPD）发生发展中的意义。方法建立吸烟大鼠COPD模型，测定大鼠的肺功能及其血清和BALF的细胞数，观察肺组织病理形态变化和肺平均内衬间隔（MLI）和平均肺泡数（MAN）评估肺气肿的程度。用酶联免疫吸附测定（ELISA）法检测大鼠血清和支气管肺泡灌洗液（BALF）中TNF—α及TNFRI的表达。结果COPD组BALF中白细胞、中性粒细胞及巨噬细胞数增高。COPD组肺功能指标FEV0．3、FEV0．3／FVC％和PEF分别为（1．86±0．22）ml、（65．064-8．40）％、（18．84±1．56）ml/s，比正常组（4．20±0．25）ml、（85．56±5．85）％、（47．24±7．28）ml／s下降。COPD组MLI、MAN分别为（77．32±28．73）um／个、（232．00±97．18）个／mm。而正常组为（43．96±7．16）um／个、（392．84±24．41）个／mm^2，COPD组MLI增加而MAN减少；COPD组血清和BALF的TNF—α、TN—FRl表达增高，分别为TNF—α（117．98±33．82）pg／ml、（155．10±27．60）pg／ml而TNFR1为（85．00±16．34）pg／ml、（98．13±11．97）pg／ml而正常组为TNF-α（73．98±16．41）ps／ml、（79．20±27．70）ps／ml，TNFR1为（58．82±24．57）pg／ml、（61．89±26．25）pg／ml。COPD组BALF的TNFR1表达与MLI呈正相关（r=0．79，P=0．004）与MAN呈负相关（r=-0．626，P=0．039）。两组间不比较均有统计学差异（P〈0．05）。结论TNF—α、TNFR1作为炎症介质在COPD的发生、发展中起重要促进作用。

The significance of Tumor necrosis factor-alpha and Tumor necrosis factor rceptor 1 in The rat model of COPD

Objective To investigate the significance of Tumor necrosis factor-alpha （TNF-α） and Tumor necrosis factor rceptor 1 （ TNFR1 ） in the pathogenesis of COPD. Methods The rats were divided into a normal control group and a COPD model group. The rat model of COPD was established by exposure to cigarette smoking. Total cell counts, neutrophil counts and neutrophil proportion in serum and brenchoalveolar lavage fluid （BALF） were examined. The lung function includes forced expiratory volume in 0. 3 secend （ FEV0.3 ） , forced expiratory volume in 0.3 secend vs forced vital capacity （ FEV0.. 3/FVC% ） and peak expiratory flow （PEF） ,pathologic changes of lung tissues were investigated. The mean linear intercept （MLI） and mean alveolar numbers （ MAN ） were determined by light microscope in order to study the degree of emphysema. The levels of TNF-α and TNFR1 in serum and BALF were measured with enzyme linked immunosorbent assay （ELISA）. Results After modeling in COPD group comparing with normal group statistic analysis showed total leukocyte counts and neutrophil counts and neutrophil proportion were increased, FEV0. 3 （4. 20 ± 0. 25 ） ml vs （ 1.86 ± 0. 22 ） ml, FEV0. 3/ FVC （ 85.56 ± 5.85 ） % vs （65.06 ± 8.40） %, PEF （47.24± 7.28 ） ml/s vs （ 18. 84 ± 1.56 ） ml/s in normal group vs COPD group respectively. FEVO. 3 ,FEV0. 3/FVC and PEF were significantly decreased in COPD group comparing with normal group （ P 〈 0. 05 ）, MLI （77. 32 ±28.73） um/n vs （43.96 ±7. 16） um/n in COPD group was higher than that in normal group while MAN （232. 00±97. 18）n/ mm^2 vs （ 392. 84 ± 24. 41 ） n/mm^2 was decreased in COPD group compared with normal group （ P 〈 0. 05 ）. The levels of TNF-α in serum and BALF（73.98 ±16.41 ） pg/ml vs （ 79.20 ± 27. 70 ） pg/ml, （ 117.98 ± 33.82 ） pg/ml vs 155.10 ± 27.60pg/ml were higher in S group than in N group. The levels of TNFR1 in serum and BALF（58. 82 ± 24. 57 ）pg/ml vs （61.89 ± 26. 25 ）pg/ml, （85.00 ± 16. 34 ） pg/ml vs （98. 13 ± 11.97 ） pg/ml were higher in S group than in N group （ all P 〈 0. 05 ）. The levels of TNFR1 in BALF revealed positive correlation to MLI but negative correlation to MAN in COPD group. Conclusion It may play an important role in the pathogenesis of COPD that TNF-α and TNFR1 are inflammatory mediators.