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低分子肝素对慢性阻塞性肺疾病大鼠模型细胞间黏附分子-1、单核细胞趋化蛋白-1表达的影响
【作者】 陈霞；
【导师】 程兆忠；
【作者基本信息】 青岛大学 ， 内科学， 2010， 硕士
【摘要】 目的观察低分子肝素(LMWH)对慢性阻塞性肺疾病(COPD)大鼠模型肺组织细胞间黏附分子-1(ICAM-1)和单核细胞趋化蛋白-1(MCP-1)表达的影响,探讨其对COPD可能的干预机制。方法将Wistar大鼠30只随机分为三组：①健康对照组(n=10)：正常喂养40天,不做任何干预；②COPD模型组(n=10)：采用熏吸香烟加气管内注入脂多糖的方法建立COPD大鼠模型；③LMWH干预组(n=10)：模型制备同前,熏烟前半小时皮下注射LMWH150u/kg,每天1次。观察各组肺组织病理改变、血气指标、肺泡灌洗液(BALF)的细胞计数及分类,应用免疫组化法测定肺组织ICAM-1、MCP-1的表达情况。结果所建COPD大鼠模型的病理学改变符合人类COPD的特点。①与健康对照组比较,COPD模型组肺组织ICAM-1、MCP-1的表达增强(P<0.01),且ICAM-1与BALF中中性粒细胞数成正比(r=0.82,t=4.00,P<0.01),MCP-1与BALF中巨噬细胞数成正比(r=0.81,t=3.96,P<0.01)。②与COPD模型组比较,LMWH干预组肺组织的病理改变轻,BALF中白细胞总数、中性粒细胞数百分比下降(P<0.01),肺组织ICAM-1、MCP-1的表达减弱(P<0.05、0.01)。结论ICAM-1、MCP-1参与气道炎症的发生,LMWH可能通过抑制ICAM-1、MCP-1表达而减轻COPD气道炎症。
【Abstract】 Objective To observe the effect of low molecular weight heparin(LMWH) on expression of intercellular adhesion molecular-1(ICAM-1) and monocyte chemoattractant protein-1(MCP-1) in lung tissue of rats with chronic obstructive pulmonary disease(COPD), then demonstrate the intervention mechanism for chronic obstructive pulmonary disease of low molecular weight heparin.Methods Thirty Wistar rats were randomly divided into three groups,with 10 in each:①normal control group:raised the rats in normal condition for forty days without any interferende;②COPD model group:The COPD model was established by intratracheal instillation of lipopolysaccharide and exposed to cigarette smoking;③LMWH treated group:model methods were the same as above, LMWH 150U/kg was given by hypodermic injection,daily, Pathologic changes of the lung tissue,blood gas and the total and differential cell counts of bronchoalveolar lavage fluid were determined.The expression of ICAM-1 and MCP-1 was observed by immunohistochemical method..Results The pathological changes in COPD model group was coincident with that in humans.①Compared with normal control group, The expression of ICAM-1、MCP-1 of lung tissue of the COPD group significantly increased (P<0.05), and ICAM-1 was positively correlated with the leukocyte numbers and neutrophils in BALF in the model group(r=0.82,t=4.00,P<0.01),MCP-1 was positively correlated with the macrophage in BALF in the model group(r=0.81, t=3.96,P<0.01);②Compared with COPD model group,pathological changes of the lung tissue in LMWH treated group decreased.The total white blood cells and the percentages of neutrophils in BALF in LMWH treated group decreased (P<0.01).The expression of ICAM-1 and MCP-1 in LMWH treated group decreased (P<0.05、0.01)Conclusion:ICAM-1 and MCP-1 may be involved in the process of airway inflammation in COPD.LMWH may decrease the expression of ICAM-1 and MCP-1 to relievate the inflammatory reaction.