关键词: 肺气肿, 阻塞性, 抗凝血酶-Ⅲ, 肿瘤坏死因子-α, 组织因子途径抑制物, 己酮可可碱

Abstract: Objective To investigate the abnormalities of coagulation and fibrinolytic system in experimental pulmonary emphysema in rats and evaluate the effects of pentoxyfylline(PTX) on inhibiting the pathogenesis of emphysema in rats.Methods Thirty-six Wistar rats were randomly divided into three groups, the normal control group, the model group and the PTX group. Rats in the model group and PTX group were injecting endotoxin(3 mg/kg) into vena caudalia on the 1^st、14^th、28^th days and exposed to the smoke from 12 pieces of cigarettes for 30 minutes in days 2～45(excluding the 14^th and 28^th days), two times a day with the intervals about 4 hours. The PTX group were treated with PTX, 15 mg/(kg·d^-1), by intraperitoneal injection before passive smoking from 1～30^th days. Observation began on the second day. Pumonary function tests were performed to evaluate the following indices including FEV_0.2, FEV_0.2/FVC, Ri, Re. After which rats of all three groups were sacrificed. The blood serum levels of TNF-α, IL-10 and the plasma levels of tPA, PAI-1, TFPI: Ag were measured by ELISA method, the blood AT-Ⅲ activity were measured by chromogenic assay,and the lung histopathological changes of all rats were observed with morphometric method with HE stain.Results Rats of the model group shared many features of human chronic obstructive pulmonary emphysema, such as infiltration of lymphocytes, monocytes and neutrophils in airways wall, distorted alveolar structure and enlarged alveoli. The extent of emphysematous damage of PTX group such as infiltration of lymphocyte in airways wall and enlarged alveoli were milder than those of the model group. Pulmonary function tests showed that the FEV_0.2/FVC of model group was greatly lower than those of the normal control group(P<0.01), but FEV_0.2/FVC of PTX group was increasingly higher than the model group(P<0.01). Compared with the normal group, the model group presented significant differences in the plasma levels of AT-Ⅲ activity, TFPI:Ag, tPA and PAI-1〔(56.04±14.81)vs(85.46±18.03), (1.39±0.26)μg/L vs(1.05±0.17)μg/L, (F=29.42,0.35,P<0.01);(2.1±0.73)μg/L vs (1.45±0.43)μg/L,(0.54±0.07)μg/L vs (0.80±0.24)μg/L, (F=0.79,0.26,P<0.05) respectively〕; there were negative correlations between AT-Ⅲ activity and TNF-α(r=-0.87,P<0.01);In comparison with the model group, TNF-α and AT-Ⅲ in the PTX group〔(10.69±2.54)pg/ml vs (21.32±5.71)pg/ml,(76.83±9.03)vs(56.04±14.81) respectively〕were also markedly improved(F=11.35, 8.84, 20.80, P<0.01).Conclusion The experimental pulmonary emphysema model in rat could be successfully established by exposing to cigarette smoke and repeated injecting endotoxin into vena caudalia. The abnormalities of coagulation and fibrinolytic system is induced by the pulmonary vascular endothelial injury. AT-Ⅲ , TFPI, tPA and PAI-1 might be involved in the process. PTX can inhibit the release of TNF-a and relieve the airway inflammation, and also enhance AT-Ⅲ and improve hypercoagulative state. It suggests that PTX can inhibit the development of pulmonary emphysema in rat.

Key words: pulmonary emphysema, obstructive pulmonary emphysema, antithrombin-Ⅲ, tumor necrosis factor-α, tissue factor pathway inhibitor, pentoxyfylline