基于MMPs/TIMPs及Th1/Th2探讨六味补气胶囊改善COPD大鼠肺功能的机制

Effects of Liu-Wei Bu-Qi Capsules on MMPs/TIMPs,Th1/Th2 among COPD Rats Accompanied with Reduced Lung Function

目的:基于MMPs/TIMPs及Th1/Th2探讨六味补气胶囊改善慢性阻塞性肺疾病(COPD)肺功能的机制。方法:将75只大鼠随机分均为正常组、模型组、六味补气组、金水宝组、脾氨肽组。除正常组外,其余大鼠均采用烟熏加脂多糖气管滴入方法建立COPD模型。模型成功第28天给药,连续给药30天。观察各组大鼠肺组织形态学、肺功能、白介素-4(IL-4)、γ干扰素(IFN-γ)、基质金属蛋白酶(MMP-9)及MMPs抑制剂1(TIMP-1)变化。结果:与正常组比较,模型组肺组织损伤、肺功能明显降低,炎性因子IL-1β、IFN-γ、Th1/Th2明显升高(P<0.05或P<0.01),抑炎因子IL-4、IL-35明显降低(P<0.05或P<0.01);肺组织MMP-9基因和蛋白表达明显升高(P<0.05或P<0.01),TIMP-1基因和蛋白表达明显降低(P<0.05或P<0.01)。药物治疗后,与模型组比较,六味补气组IFN-γ、Th1/Th2明显降低(P<0.05或P<0.01),MMP-9基因及蛋白表达明显降低(P<0.05或P<0.01),TIMP-1表达明显升高(P<0.05或P<0.01);与金水宝组、脾氨肽组比较,六味补气组肺功能、TIMP-1基因蛋白表达升高,MMP-9、Th1/Th2表达明显降低(P<0.05)。结论:六味补气胶囊通过上调IL-4、TIMP-1,下调IFN-γ、Th1/Th2、MMP-9表达,降低炎性反应,改善COPD肺功能。

This article was aimed to study the mechanism of Liu-Wei Bu-Qi （LWBQ） Capsules among rat models of chronic obstructive pulmonary disease （COPD） accompanied with reduced lung function based on MMPs/TIMPs and Th1/Th2. A total of 75 rats were randomly divided into the normal group, model group, LWBQ group, Jin-Shui-Bao （JSB） group, spleen aminopeptidase group. Except the normal group, smoke plus lipopolysaccharide tracheal instil-lation method was applied among rats in other groups to establish COPD rat model. Medication was given on the 28th day after the model was established. The medication was given for 30 days. Observation was given on changes of lung histology, lung function, interleukin （IL）-4, interferon-γ （IFN-γ）, matrix metalloproteinases （MMP-9） and MMPs inhibitor 1（TIMP-1）. The results showed that compared with the normal group, in the model group, lung tis-sues was damaged, and lung function was obviously reduced, while the level of inflammatory factor such as IL-1β, IFN-γ, Th1/Th2 were obvious increased （P〈 0.05 or P〈 0.01）; while inflammation-inhibiting factors such as IL-4 and IL-35 were obviously decreased （P 〈 0.05 or P 〈 0.01）; MMP-9 gene and protein expression of lung tissues were obviously increased （P〈 0.05 or P〈 0.01）; TIMP-1 gene and protein expression were obviously decreased （P〈 0.05 or P 〈 0.01）. After medication, compared with the model group, in the LWBQ group, IFN-γ and Th1/Th2 were obviously decreased （P〈 0.05 or P〈 0.01）; MMP-9 gene and protein expression were obviously decreased （P〈 0.05 or P 〈 0.01）; TIMP-1 expression was obviously increased （P 〈 0.05 or P 〈 0.01）. Compared with the JSB group and spleen aminopeptidase group, the lung function and TIMP1 gene protein expression were increased, while MMP-9 and Th1/Th2 expression were obviously decreased （P 〈 0.05）. It was concluded that LWBQ Capsules up-regulate IL-4 and TIMP-1, downregulate IFN-γ, Th1/ Th2 and MMP-9 expression, in order to reduce inflammatory response and improve lung function among COPD cases.