大鼠发展至COPD过程中凝血纤溶指标变化

THE CHANGES OF COAGULATION AND FIBRINOLYTIC SYSTEM IN THE PROGRESS OF A RAT BECOMES CHRONIC OBSTRUCTIVE PULMONARY DISEASE

目的观察大鼠发展至慢性阻塞性肺疾病(COPD)过程中各时期凝血、纤溶指标变化。方法将Wistar大鼠50只随机分为正常对照组和COPD造模1周组、2周组、3周组、4周组,每组10只。采用熏吸香烟加气管内注入脂多糖的方法建立COPD模型。观察各组肺组织病理改变,用BE-Compact全自动凝血分析仪测定血浆凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)和纤维蛋白原(FIB)、血浆抗凝血酶Ⅲ(AT-Ⅲ)水平,应用酶联免疫吸附法(ELISA)测定血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI-1)和D-二聚体(D-dimer)水平。结果 4周组大鼠病理学改变符合人类COPD的特点,1～3周组大鼠肺组织病理分别符合急性支气管炎、慢性支气管炎、肺气肿期的病理改变。1周组大鼠PT、TT、ATⅢ、APTT、FIB、PAI-1t、PA、D-dimer水平较对照组无明显差异(P>0.05);2周组、3周组大鼠FIB、PAI-1、D-dimer水平较对照组升高,而ATⅢt、PA水平较对照组降低(F=8.52～18.90,q=3.46～6.55,P<0.05、0.01);4周组大鼠FIB、PAI-1、D-dimer水平较对照组升高,PT、APTT、ATⅢ、tPA水平较对照组降低(F=6.61～105.79,q=4.71～17.14,P<0.01)。结论 COPD大鼠存在血栓前状态,在大鼠形成COPD之前其体内的凝血纤溶系统处于失衡状态。

Objective To observe the changes of index of coagulation and fibrinolytic system in the progress of a rat to become chronic obstructive pulmonary disease（COPD）. Methods Fifty Wistar rats were equally randomized to normal control,1-week-,2-week-,3-week-,and 4-week-COPD group.A model of COPD in rats was created by exposure in cigarette smoking and intratracheal instillation of lipopolysaccharide.The pathology of lung tissue in each group was observed;PT,FIB,TT,APTT and ATⅢ were determined by BE-Compact automated blood coagulation analyzer;The blood plasma levels of tPA,PAI-1 and D-dimer were measured by ELISA method. Results The 4-week group was consistent with the rat COPD model,its pathological changes were in line with the features of COPD in man.The pathology of lung tissues of rats in 1-week-to 3-week-group was consistent with acute bronchitis,chronic bronchitis and emphysema,respectively.In 1-week-COPD,PT,TT,ATⅢ,APTT,FIB,PAI-1,tPA,and D-dimer were not significantly different as compared with the control（P0.05）;In 2-week-COPD and 3-week-COPD,the levels of FIB,PAI-1 and D-dimer were higher than that in the control（P0.05,0.01）,while ATⅢ and tPA were lower（P0.01）;In 4-week-COPD,the levels FIB,PAI-1 and D-dimer were higher than that in the control（P0.01）,while PT,APTT,ATⅢ,and tPA were lower（P0.01）. Conclusion Pre-thrombus state is existent in COPD rats.The coagulation and fibrinolytic system in rats are unbalanced before they are involved in COPD.