1. 上海中医药大学基础医学院,上海,201203
2. 上海中医药大学科技实验中心,上海,201203
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丁亚杰, 陈晓, 俞仲毅, 等. 芩麻方对慢性阻塞性肺疾病模型大鼠气道重塑作用影响的实验研究[J]. 上海中医药杂志, 2017,51(8):77-81.
DING Ya-jie, CHEN Xiao, YU Zhong-yi, et al. Experimental study of effects of Qinma Formula on airway remodeling in rats with chronic obstructive pulmonary disease[J]. Shanghai Journal of Traditional Chinese Medicine, 2017,51(8):77-81.
丁亚杰, 陈晓, 俞仲毅, 等. 芩麻方对慢性阻塞性肺疾病模型大鼠气道重塑作用影响的实验研究[J]. 上海中医药杂志, 2017,51(8):77-81. DOI:
DING Ya-jie, CHEN Xiao, YU Zhong-yi, et al. Experimental study of effects of Qinma Formula on airway remodeling in rats with chronic obstructive pulmonary disease[J]. Shanghai Journal of Traditional Chinese Medicine, 2017,51(8):77-81. DOI:
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 the rat model of chronic obstructive pulmonary disease(COPD),investigate the mechanism of airway remodeling induced by imbalance of protease and protease inhibitors in COPD and study the effects and possible mechanism of Qinma Formula in the treatment of COPD. Methods 70 SPF rats were randomly divided into the normal group,model group,Qinma Formula groups with low-,middle- and high-dose,Liujunzi Decoction group and aminophylline group,10 rats in each group. Rat model of COPD was established by intratracheal injection of pyrosulfuryl chloride solution and mixture of lipopolysaccharide and pepsin combined with smoking. The respiratory function of rats was measured by noninvasive respiratory function apparatus. The morphology of lung tissue and bronchus were observed under light microscope. The serum content of transforming growth factor-β,1, (TGF-β,1,) was detected by ELISA. The expressions of matrix metalloproteinases-9(MMP-9)and tissue inhibitor of metalloproteinnase-1(TIMP-1)in lung tissue were determined by immunohistochemistry. Results: Compared with the model group,Qima Formula could significantly decrease the respiratory frequency(P,<,0.05),and increase the respiratory flow(P,<,0.05). The thickness of airway wall and smooth muscle were significantly decreased in the Qinma Formula groups with middle-and high-dose(P,<,0.05).The serum content of TGF-β,1, was significantly decreased in the Qinma Formula groups with low-,middle- and high-dose(P,<,0.05).The expressions of MMP-9 and TIMP-1 were significantly decreased in the Qinma Formula groups with middle- and high-dose(P,<,0.05). Conclusion: Qinma Formula could significantly improve the respiratory function of rats and down-regulate the expressions of MMP-9 and TGF-β,1, in lung tissue,and thus reduce the destruction on alveolar and tracheal structures and reverse the airway remodeling.
芩麻方慢性阻塞性肺疾病气道重塑转化生长因子β1基质金属蛋白酶-9基质金属蛋白酶抑制剂-1
Qinma Formulachronic obstructive pulmonary diseaseairway remodelingTGF-β1MMP-9TIMP-1
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