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

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (9): 985-990.

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

刘雅丽¹, 张立², 金海燕³, 安淑华⁴

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

收稿日期:2008-07-23 修回日期:2008-08-30 出版日期:2008-09-26 发布日期:2020-10-13
作者简介:刘雅丽, 女, 博士, 副主任医师, 研究方向:临床免疫。Tel:0571-81719682 E-mail:Wjyliu@163.com
基金资助:
杭州市医药卫生科技计划项目(2004A003)

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-li¹, ZHANG Li², JIN Hai-yan³, AN Shu-hua⁴

¹First People's Hospital of Hangzhou, Hangzhou 310000, Zhejiang, China;
²Children's Hospital Attached to the Capital Institute of Peadiatrics, Beijing 100010, China;
³Department of Anesthesiology, Children's Hospital of Zhejiang Province, Hangzhou 310000, Zhejiang, China;
⁴Hebei Provincial Children's Hospital, Shijiazhuang 050000, Hebei, China

Received:2008-07-23 Revised:2008-08-30 Online:2008-09-26 Published:2020-10-13

摘要/Abstract

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

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.

Key words: asthma, metalloproteinases-9(MMP-9), tissueinhibitorofmetalloproteinase(TIMP-1), airwayremodeling, anti-RANTESantibody

中图分类号:

R965.2

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]. 中国临床药理学与治疗学, 2008, 13(9): 985-990.

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]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(9): 985-990.

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