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目的建立慢性阻塞性肺疾病(COPD)大鼠模型,探究COPD发病过程中蛋白酶与蛋白酶抑制剂失衡导致气道重塑的机制,探讨芩麻方治疗COPD的效果和可能的作用机制。方法将70只SPF级大鼠随机分为正常组,模型组,芩麻方低、中、高剂量组,六君子汤组及氨茶碱组,每组10只。除正常组外,采用气管内注入二硫酰氯溶液以及脂多糖和胃蛋白酶的混合物,联合烟熏造模方法制备COPD大鼠模型。无创呼吸功能测定仪测定大鼠呼吸功能。光镜下观察大鼠肺组织和支气管形态。ELISA法检测血清中转化生长因子β_1(TGF-β_1)的含量。免疫组化法检测支气管肺组织中的基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)表达的变化。结果与模型组比较,芩麻方能显著降低呼吸频率(P<0.05),加大呼吸流量(P<0.05)。芩麻方中、高剂量组气管壁厚度和平滑肌厚度显著降低(P<0.05);芩麻方低、中、高剂量组血清TGF-β_1含量显著降低(P<0.05)。芩麻方中、高剂量组MMP-9和TIMP-1的含量显著降低(P<0.05)。结论芩麻方能显著改善大鼠呼吸功能,下调肺组织中MMP-9以及TGF-β_1的表达,从而减轻其对肺泡、气管结构的破坏,逆转气道重塑的发生。
Objective To establish a rat model of chronic obstructive pulmonary disease (COPD) and investigate the mechanism of airway remodeling caused by the imbalance of protease and protease inhibitor during the pathogenesis of COPD and to explore the effect and possible mechanism of Scutellaria maxima in the treatment of COPD. Methods Seventy SPF rats were randomly divided into normal group, model group, low, medium and high dose Qinqianfang group, Liujunzitang group and aminophylline group, 10 rats in each group. In addition to the normal group, a rat model of COPD was prepared by intratracheal instillation of a dithioyl chloride solution and a mixture of lipopolysaccharide and pepsin in combination with smoking modeling. Noninvasive respiratory function detector for measuring respiratory function in rats. The lung tissue and bronchial morphology were observed under light microscope. Serum levels of TGF-β 1 were detected by ELISA. The expression of MMP-9 and TIMP-1 in bronchial lung tissue was detected by immunohistochemistry. Results Compared with model group, Scutellariae could significantly reduce respiratory rate (P <0.05) and increase respiratory flow (P <0.05). The contents of TGF-β 1 in serum of Qinmafang medium and high dose groups were significantly decreased (P <0.05). The contents of MMP-9 and TIMP-1 in Qincui medium and high dose groups were significantly decreased (P <0.05). Conclusions Scutellaria sinensis can significantly improve the respiratory function of rats and down-regulate the expression of MMP-9 and TGF-β 1 in lung tissue, so as to reduce the destruction of alveolar and tracheal structure and reverse the occurrence of airway remodeling.