己酮可可碱对实验性阻塞性肺气肿大鼠凝血纤溶系统的影响  

The Abnormalities of Coagulating and Fibrinolytic System and the Effects of Pentoxifylline on Coagulating and Fibrinolytic Function in Experimental Obstructive Pulmonary Emphysema in Rats

作　　者：李远红[1] 张洪玉[2] 庞宝森[2] 陈阳育[2] 毛燕玲[2] 马力[2] 黄秀霞[2] 辛萍[2] 张海燕[2] 

机构地区：[1]首都医科大学附属北京朝阳医院皮肤科 [2]首都医科大学附属北京朝阳医院呼吸病研究所

出　　处：《首都医科大学学报》2007年第5期627-631,共5页Journal of Capital Medical University

摘　　要：目的：观察实验性阻塞性肺气肿大鼠的凝血纤溶系统失衡状态及评价己酮可可碱（PTX）对实验性阻塞性肺气肿大鼠的防治效果,并探讨其机制。方法：36只Wistar大鼠分为3组,正常对照组、模型组和治疗组（每组12只）。模型组、治疗组大鼠第1、14、28天经尾静脉注射内毒素3mg/kg,第2～45天（第14、28天除外）每日被动吸烟2次,每次12支,持续30min,两次吸烟之间间隔4h,大鼠模型制备过程共45d。PTX治疗组每天熏烟前30min腹腔内注射PTX15mg/kg,连续30d。实验结束后,观察各组大鼠的肺功能情况,用酶联免疫吸附法（ELISA）测定血清中肿瘤坏死因子α（TNF-α）、白细胞介素10（IL-10）、组织型纤溶酶原激活剂（tPA）、纤溶酶原激活物抑制剂-1（PAI-1）、血浆组织因子途径抑制物抗原（TFPI：Ag）的含量,发色底物法测定血浆抗凝血酶-Ⅲ（AT-Ⅲ）活性,并进行HE染色观察肺脏病理改变。结果：模型组大鼠肺功能指标第0.2秒用力呼出容积占用力肺活量百分比（FEV0.2/FVC）与正常对照组（88.52±2.09）比较,差异有统计学意义（P〈0.01,P〈0.05）;模型组大鼠AT-Ⅲ和TFPI与正常对照组比较,差异有统计学意义（P均〈0.01）;模型组大鼠tPA和PAI-1与正常对照组比较,差异有统计学意义（P均〈0.05）。经直线相关分析发现,模型组大鼠AT-Ⅲ与TNF-α负相关（r=-0.87,P〈0.01）;PTX组FEV0.2/FVC、TNF-α和AT-Ⅲ与模型组比较,差异有统计学意义（P均〈0.01）。组织学观察显示模型组大鼠支气管管壁及周围大量的炎性细胞浸润;肺泡结构紊乱,肺泡腔扩大。PTX组炎性细胞浸润以及肺泡腔扩大情况较模型组减轻。结论：采用熏香烟加尾静脉注射内毒素的方法,可成功复制大鼠阻塞性肺气肿模型。模型组大鼠肺血管内皮细胞受损,体内的凝血纤溶系统存在失衡状态,AT-Ⅲ、TFPI、tPA和PAI-1可能参与这一过程。PTX能阻止白细胞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 FEV0.2, FEV0.2/ 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 FEV0.2/FVC of model group was greatly lower than those of the normal control group（ P 〈 0.01 ）, but FEV0.2/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, TFP

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 

分 类 号：R563.3[医药卫生—呼吸系统]