低分子肝素对COPD模型大鼠MMP-9及TIMP-1影响

EFFECTS OF LOW MOLECULAR HEPARIN ON MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITORS OF METALLOPROTEINASE-1 IN LUNG TISSUE OF RAT MODEL WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

目的观察低分子肝素(LMWH)对慢性阻塞性肺疾病(COPD)大鼠模型肺组织基质金属蛋白酶-9(MMP-9)及组织金属蛋白酶抑制物-1(TIMP-1)表达的影响,探讨其对COPD可能的干预机制。方法随机将30只Wistar大鼠分成3组,每组10只。对照组大鼠正常饲养40 d,不做任何干预;COPD模型组大鼠用香烟染毒加气管内注入脂多糖法建立COPD模型并给予生理盐水皮下注射,每天1次;LMWH干预组大鼠造模后给予低分子肝素150 U/kg皮下注射,每天1次,治疗40 d。观察3组血气、肺组织病理学改变,采用免疫组织化学法检测肺组织MMP-9和TIMP-1表达。结果LMWH干预组大鼠肺组织的病理改变程度减轻,MMP-9表达减少,其阳性面积及MMP-9/TIMP-1与COPD模型组比较差异有显著意义(F=6.39、56.04,q=26.72、3.34,P<0.01)。结论LMWH可能通过调节MMP-9、TIMP-1表达,减轻肺气肿时肺泡壁破坏过程中细胞外基质的降解,发挥治疗COPD的作用。

Objective To observe the effects of low molecular heparin （LMH） on expressions of matrix metalloproteinase-9 （MMP 9） and tissue inhibitors of metalloproteinase-1 （TIMP-1） in lung tissue of Wistar rats with chronic obstructive pulmonary disease （COPD） and the possible intervention mechanism of this condition. Methods Thirty Wistar rats were equally randomized to control group： normally raised for 40 days without any interference; COPD model group： cigarette inhalation plus intratracheal instillation of lipopolysaccharide and hypodermic injection of normal saline, once a day; LMH group： LMH, 150 U/kg, hypodermic injection, once a day for 40 days. Blood gas, histology of lung tissue, and MMP-9/TIMP-1 expressions were examined. Results Pathological changes of the lung tissue in LMH decreased, compared with COPD model group, the diffe rences of expression of MMP 9 and the ratio of MMP-9/TIMP-1 were significantly different （F= 6.39,56.04;q-26.72,3.34;P〈0.01）. Conclusion Low molecular heparin educes its effect on therapy of COPD probably by regulating the expressions of MMP 9 and TIMP-1, lessening the degradation of extracellular matrix in the process of destruction of extracellular matrix of alveolar wall when emphysema happened.