益气化瘀化痰法对肺纤维化大鼠肺组织结构及血清MMP-9、TIMP-1的影响

目的 观察益气化瘀化痰法(YHH)对肺纤维化大鼠肺组织结构、血清基质金属蛋白酶-9(MMPO)和金属蛋白酶组织抑制物-1(TIMP-1)水平的影响,探讨其防治肺纤维化的可能机制.方法 健康SD大鼠采用博来霉素建立肺纤维化模型,随机分成7组:正常对照组(Z组)、模型组(M组)、氢化可的松组(QK组)、益气组(YQ组)、化瘀组(HY组)、化痰组(HT组)、益气化瘀化痰组(YHH组).HE、Masson染色光镜观察肺组织病理形态变化;电镜观察肺组织超微结构变化;酶联免疫吸附法(ELISA)检测血清MMP-9、TIMP-1含量.结果 1)与M组比较,各治疗组均能减少肺间质胶原沉积,减轻肺纤维化程度,尤以YHH组较为明显2)与Z组比较,M组血清MMP-9水平有所升高,TIMP-1水平显著升高,MMP-9/TIMP-1比值降低(P＜0.05);与M组比较,各治疗组均能升高血清MMP-9水平,降低TIMP-1水平,升高MMP-9/TIMP-1比值,以YHH组作用更显著(P＜0.05).结论 益气化瘀化痰法可能在一定程度上通过调整MMP-9/TIMP-1的比值,使其趋于平衡,从而延缓肺纤维化的进程.

Effect of Tonifying Qi and Resolving Stasis and Phlegm on Pulmonary Histopathology and Concentration of MMP-9, TIMP-1 in Serum on Bleomycin Induced Pulmonary Fibrosis Rats

Objective To study the effects of the method of Tonifying qi ,resolving stasis and phlegm （YHH） on the pulmonary Histopathology and concentration of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of matrix metalloproteinase-1 （ TIMP-1 ） in pulmonary fibrosis rats. Methods SD rats were randomly divided into： the normal, the model,the hydrocortisone, the tonifying qi, the resovling stasis, the resolving phlegm and the Tonifying qi, resolving stasis and phlegm group. The model rats were established with the method of intratracheal injection of bleomycin. The pathological changes of lung tissues were observed by lightmicroscopy and electron microscopy. The levels of MMP-9 and TIMP-1 in serum were detected by Enzyme-linked immunosorbent assay（ELISA）. Results 1 ） Compared with the model group, the hydrocortisone group and the four combinations of tonifyiung qi, resolving stasis and resolving phlegm could reduce the collagen sediment in the interstitial,the results in YHH group is the best. 2） Compared with the normal group,the levels of MMP-9 increased,however,the levels of TIMP-1 increased significantly resulting in the lower ratio of MMP-9 to TIMP-1 （ P 〈 0. 05 ）. Compared with the model group, the levels of MMP-9 in serum of YHH group of mice elevated,while the levels of TIMP-1 went down significantly causing the higher ratio of MMP-9 to TIMP-1 （ P 〈 0.05）. Conclusion The method of YHH may delaying the progress of interstitial pulmonary fibrosis through regulating the ratio of MMP-9 and TIMP-1.