MMP-9、TIMP-1分别对哮喘小鼠和气道重塑小鼠作用的比较研究  

The comparision of effect of MMP-9 and TIMP-1 between murine model of asthma and murine model of airway remodeling

作　　者：朱建明[1] 白建文[1] 林闽加[1] 

机构地区：[1]上海同济大学附属东方医院急诊医学部,200120

出　　处：《临床肺科杂志》2009年第6期775-777,共3页Journal of Clinical Pulmonary Medicine

摘　　要：目的研究基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和基质金属蛋白酶抑制剂-1(tissue inhibitor matrix metalloproteinase-1,TIMP-1)在小鼠哮喘模型和气道重塑模型中表达作用的区别。方法30只BALB/c雌性小鼠按随机数字表法分为哮喘组(n=10)、气道重塑组(n=10)和生理盐水对照组(n=10)。通过鸡卵清白蛋白(ovabumin,OVA)滴鼻和腹腔注射的的方法分别建立小鼠哮喘模型和气道重塑模型。通过病理学观察气道炎症和气道重塑。用免疫组化法测定MMP-9和TIMP-1蛋白的表达;RT-PCR测定MMP-9和TIMP-1的基因水平表达。结果病理学显示哮喘组气道痉挛,大量炎性细胞浸润;气道重塑组呈现气道上皮指状增生,管腔内容物增多,上皮下纤维化。免疫组化结果显示哮喘组MMP-9为8868.8±3544.5,TIMP-1为4783±1508.1,二者比值为1.85;气道重塑组MMP-9为4383.1±2498.6,TIMP-1为6542.3±3026.6,气道重塑组MMP-9/TIMP-1的比值为0.67。二者有统计学意义(P<0.01)。RT-PCR结果显示气道重塑组MMP-9 mRNA的表达低于哮喘组,而气道重塑组TIMP-1 mRNA的表达高于哮喘组。结论MMP-9主要在哮喘气道炎症中表达增高,而TIMP-1则在气道重塑过程中表达升高,二者的比例失调可能是哮喘的发病机制之一。Objective To investigate whether it is different about the expression of MMP- 9 and TIMP-1 between murine model of asthma and murine model of airway remodeling. Method Thirty female BALB/c mice were randomly divided into asthma group（ n = 10）, airway remodeling group （n = 10）and control group（ n = 10 ）. The BALB/c mice were induced by OVA via peritoneal injection and intnmasal instillation. Immunohistochemistry assays was used to determine the status of MMP-9 and TIMP-1 expression in lung. RT-PCR were adopted to determine the status of MMP-9 and TIMP-1 mRNA in lung. Result Asthma group showed airway spasm and infiltration of inflammatory cells. But airway remodeling group showed epithelial cells with finger-like hyperplasia,increased luminal contents and subepi-thelial fibrosis. Immunohistochemistry assays suggested that MMP-9/TIMP-1 existed difference between asthma group and airway remode- ling group（ P 〈0. 01 ）. RT-PCR showed that expression of MMP-9 mRNA was higher in asthma group and TIMP-1 mRNA was higher in airway remodeling. Conclusion The expression of MMP-9 was increased in asthma model, but the expression of TIMP-1 rised in airway remodeling model. The imbalance of MMP-9/TIMP-1 may be one of the machanism of asthma disease.

关 键 词：哮喘 气道重塑 基质金属蛋白酶-9 基质金属蛋白酶抑制剂-1 

分 类 号：R562.25[医药卫生—呼吸系统]