MMP-9及TIMP-1在支气管哮喘发病中作用及雷公藤多甙干预研究

Study on the role of MMP-9 and TIMP-1 in the pathogenesis of asthmatic rates and the interfering effects of tripterygium polyglucoside

目的观察支气管哮喘(简称哮喘)大鼠肺组织中细胞外基质(ECM)代谢相关因子基质金属蛋白酶9(MMP-9)及其抑制剂组织金属蛋白酶抑制剂1(TIMP-1)的表达,研究雷公藤多甙在哮喘肺组织ECM重塑中可能的作用及其机制。方法建立大鼠哮喘模型,采用逆转录-聚合酶链反应技术(RT-PCR)测定肺组织中MMP-9、TIMP-1mRNA的表达。结果哮喘组MMP-9、TIMP-1在肺组织中的蛋白表达明显高于对照组(P<0·01),应用药物雷公藤多甙干预后,MMP-9、TIMP-1蛋白表达明显低于哮喘组(P<0·05)。哮喘组MMP-9、TIMP-1在肺组织的mRNA表达也高于对照组(P<0·01),应用雷公藤多甙药物干预后,MMP-9、TIMP-1在肺组织的mRNA表达明显低于哮喘组(P<0·01)。哮喘组肺组织中MMP-9/TIMP-1>1,明显高于对照组(P<0·05),应用药物雷公藤多甙干预后,MMP-9/TIMP-1<1,明显低于对照组(P<0·05)和哮喘组(P<0·01)。结论雷公藤多甙可能下调MMP-9的表达,调节MMP-9/TIMP-1的平衡,干预细胞外基质重塑。

Objective To observe the effect of tripterygjitotorum on the expression of metalluproteinase-9 （ MMP-9 ） and tissue inhibitor of metalloproteinase-1 （ TIMP-1 ） in the lung of asthmatic rat. Methods Asthmatic model was established by using rats. The protein expressions of MMP-9 and TIMP-1 in lung tissue were examined by immunohistochemical analysis by reverse transcription-polymerase chain reaction （RT-PCR）. Results The protein expressions of MMP-9 and TIMP-1 in lung tissue in the asthmatic group were higher than those in the control group （ P 〈0.01 ）. After intervention with tripterygiitotorum, the protein expressions of MMP-9 and TIMP-1 in lung tissue were lower in the control group than those in the asthmatic group （ P 〈 0. 05 ）. The mRNA expressions of MMP-9 and TIMP-1 in lung tissue in asthmatic group increased significantly more than those the in control group （P 〈0. 01 ）. After treatment with tripterygiitoto- rum, the mRNA expressions of MMP-9 and TIMP-1 in lung tissue were lower in the control group than those in asthmatic group （ P 〈 0. 01 ）. In comparison with the control group, the asthmatic group presented a significant increase in the ratio of MMP-9/TIMP-1 （ P 〈 0. 05 ）, but the ratio in the drug group was lower than that in the control group （ P 〈 0. 05 ） and than that in the asthmatic group （ P 〈 0. 01 ）. Conclusion Tripterygiitotorum may influence the remodelling of extracelluar matrix by downregnlating the expression of MMP-9 and regulating the balance between MMP-9 and TIMP-1.