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

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。

Effects of metalloproteinases-9 and tissue inhibitor of metalloproteinase on airway remodeling and the intervention effect of anti-RANTES antibody in rats with asthma

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.