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MMP-9/TIMP-1 在哮喘气道重塑中的作用及抗-RANTES 抗体的干预作用
引用本文:刘雅丽,张立,金海燕,安淑华.MMP-9/TIMP-1 在哮喘气道重塑中的作用及抗-RANTES 抗体的干预作用[J].金属学报,2008,13(9):985-990.
作者姓名:刘雅丽  张立  金海燕  安淑华
作者单位:1.浙江省杭州市第一人民医院, 杭州310000, 浙江;2.北京市首都儿科研究所附属儿童医院, 北京100010;3.浙江省儿童医院麻醉科, 杭州310000, 浙江;4.河北省儿童医院, 石家庄050000, 河北
基金项目:杭州市医药卫生科技计划项目(2004A003)
摘    要:目的:通过抗-RANTES 抗体对细胞外基质(ECM) 代谢相关因子基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶抑制剂-1 (TIMP-1) 表达的影响, 探讨抗-RANTES 抗体对哮喘气道重塑的干预机制。方法:雄性Wistar 大鼠36 只, 随机分为3组:生理盐水对照组(对照组)、卵蛋白致敏及激发的哮喘组(哮喘组)、抗-RANTES 抗体干预组(干预组) 。肺组织切片用免疫组化法标记MMP-9、TIMP-1, 并用图像分析MMP-9、TIMP-1 表达水平,用ELISA 方法测定RANTES 。结果:哮喘组肺组织中MMP-9、TIMP-1 表达水平明显高于对照组(P<0.05), MMP-9/TIMP-1 比值下降, RANTES 与MMP-9/TIMP-1 呈负相关;抗-RANTES 抗体干预后MMP-9、TIMP-1 明显下降(P<0.05), MMP-9/TIMP-1 逐渐恢复, 与对照组比较无统计学差异(P<0.05);干预组气道炎症等病理学变化较哮喘组明显减轻, 临床症状明显改善。结论:抗-RANTES抗体可调节哮喘大鼠肺组织MMP-9/TIMP-1 比例的平衡, 干预细胞外基质重塑, 延缓哮喘气道重塑的发生。

关 键 词:哮喘  基质金属蛋白酶-9  基质金属蛋白酶抑制剂-1  气道重塑  抗-RANTES抗体  
收稿时间:2008-07-23
修稿时间:2008-08-30

Effects of metalloproteinases-9 and tissue inhibitor of metalloproteinase on airway remodeling and the intervention effect of anti-RANTES antibody in rats with asthma
LIU Ya-li,ZHANG Li,JIN Hai-yan,AN Shu-hua.Effects of metalloproteinases-9 and tissue inhibitor of metalloproteinase on airway remodeling and the intervention effect of anti-RANTES antibody in rats with asthma[J].Acta Metallurgica Sinica,2008,13(9):985-990.
Authors:LIU Ya-li  ZHANG Li  JIN Hai-yan  AN Shu-hua
Affiliation:1.First People's Hospital of Hangzhou, Hangzhou 310000, Zhejiang, China;2.Children's Hospital Attached to the Capital Institute of Peadiatrics, Beijing 100010, China;3.Department of Anesthesiology, Children's Hospital of Zhejiang Province, Hangzhou 310000, Zhejiang, China;4.Hebei Provincial Children's Hospital, Shijiazhuang 050000, Hebei, China
Abstract:AIM: To observe the effects of anti-RANTES antibody on the expression of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) in the lung tissue of asthma model, and study the intervention mechanism.METHODS: 36 male rats were randomly divided into three groups:control group, asthma group, and anti-RANTES antibody treated group.The immunohistochemistry method was used for marking the MMP-9 and TIMP-1 in the lung histological section and the mean optical densities of MMP-9 and TIMP-1 were measured by multifunction color patho-image analysator.The level of RANTES was detected by ELISA.RESULTS: The expression of MMP-9 and TIMP-1 in asthma group were increased significantly than those in control group (P<0.05), and the ratio of MMP-9/TIMP-1 was decreased.The expression of MMP-9 and TIMP-1 in the anti-RANTES antibody treated group were decreased significantly than those of control group (P<0.05), and the ratio of MMP-9/TIMP-1 was revived gradually, and there were no statistical significance compare with that of control group (P>0.05).The pathology changes of airway inflammation, epithelial hyperplasia and collogen deposit were decreased significantly than those of asthma group.CONCLUSION: The anti-RANTES antibody leads to decreasing the expression of MMP-9 and TIMP-1 in the lung tissue of asthma rats and adjusts the balance of the MMP-9 and TIMP-1, interferes in matrix remodeling, and plays an important role in delaying development of asthma airway remodeling.
Keywords:asthma  metalloproteinases-9(MMP-9)  tissueinhibitorofmetalloproteinase(TIMP-1)  airwayremodeling  anti-RANTESantibody  
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