COPD大鼠血栓前状态不同阶段低分子肝素抗凝观察  

EFFECTS OF LOW MOLECULAR WEIGHT HEPARIN ON DIFFERENT PERIODS OF PRETHROMBOTIC STATE IN RATS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

作　　者：王艳青[1] 孙妮娜[1] 程兆忠[1] 佟丽[1] 韩伟忠[1] 

机构地区：[1]青岛大学医学院附属医院呼吸内科,山东青岛266003

出　　处：《青岛大学医学院学报》2013年第3期243-245,248,共4页Acta Academiae Medicinae Qingdao Universitatis

基　　金：青岛市科技发展指导计划项目(KZJ-23)

摘　　要：目的观察低分子肝素(LMWH)对慢性阻塞性肺疾病(COPD)模型大鼠血栓前状态不同时期干预后凝血、纤溶指标的变化,寻找抗凝治疗最佳干预时机。方法 Wistar大鼠40只随机分为健康对照组、COPD模型组、LMWH 2周和4周干预组,每组10只。健康对照组大鼠正常喂养,不做任何干预;COPD模型组大鼠采用香烟熏染加气管内注射脂多糖法建立COPD模型并给予生理盐水皮下注射,每天1次,持续10d;LMWH 2周和4周干预组分别于造模2周、4周给予LMWH 150U/kg皮下注射,每天1次,疗程10d。观察各组大鼠肺组织病理改变,凝血、纤溶及动脉血气指标变化。结果与COPD模型组比较,LMWH干预组大鼠肺组织病理改变减轻,血浆纤维蛋白原(FIB)、纤溶酶原激活物抑制因子1(PAI-1)、D-二聚体含量显著降低(F=16.60～40.02,q=3.29～11.57,P<0.05),血浆抗凝血酶Ⅲ(AT-Ⅲ)含量显著增高(F=22.84,q=6.53,P<0.01),动脉血气改善;LMWH 2周干预组与4周干预组比较,血浆FIB、PAI-1、D-二聚体含量显著降低(q=3.03～3.67,P<0.05),AT-Ⅲ、血浆组织型纤溶酶原激活剂(t-PA)含量显著增高(F=22.84、10.02,q=2.25、4.22,P<0.05),动脉血气改善。结论大鼠COPD造模2周时,凝血、纤溶指标开始改变,可能为抗凝最佳干预时机,此时应用抗凝药物可取得更好治疗效果。Objective To observe the effects of low molecular weight heparin （LMWH） on different periods of pre- thrombotic state in chronic obstructive pulmonary disease （COPD） rat model, and look for the best time for the use of LMWH. Methods Forty Wistar rats were evenly randomized to four groups as normal control, COPD model, LMWH-2-week-intervention （2-week group） and LMWH-4-week-intervention （4-week group）. The rats in normal control group were fed normally without any interference; in COPD model group, a COPD model was created by cigarette inhalation plus intratracheal instillation of lipopolysac- charide, and hypodermic injection of normal saline was offered,once a day for 10 days; those in 2-week and 4-week groups were given subcutaneous LMWH （150 U/kg）, once a day for 10 days, starting from two and four weeks after completion of the models. The pathology of rat lung tissue, blood dotting, fibrinolysis and arterial blood gas were observed. Results Compared with the model group, the pathological changes in LMWH groups reduced, FIB, PAI 1, d-dimer significantly declined （F=16.60--40.02, q：3.29--11.57,P〈0.05）, AT-HI increased （F=22.84,q=6.53,P〈0.01）, and arterial blood gas improved. Compared with 4 week group, FIB, PAI-1, and d-dimer in 2 week group declined （q = 3.03--8.67, P〈0.05）, AT-Ⅲ and t-PA eleva ted （F = 22.84, 10.02;q=2.25,4.22 ;P〈0.05）, arterial blood gas improved. Conclusion This study showed that blood coagulation and fibrino- lytic indexes began to change two weeks after completion of rat COPD model, which is likely to be the best opportunity for antieo- agulation therapy, using anticoagulant at this time can get better therapeutic effect.

关 键 词：肺疾病 慢性阻塞性 肝素 低分子量 高凝状态 大鼠 

分 类 号：R563.9[医药卫生—呼吸系统]