二陈汤加味对慢性阻塞性肺疾病大鼠信号转导蛋白Smad3,4,6,7基因表达的影响

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目的:观察二陈汤加味对慢性阻塞性肺疾病(COPD)大鼠肺组织中信号转导蛋白Smads的影响,探讨二陈汤加味对COPD作用的机制。方法:将50只SD大鼠随机分5组,每组10只动物,包括正常组、模型组、二陈汤加味低、中、高剂量(5,10,20 g·kg~(-1)·d~(-1))组。以烟熏加气管滴注脂多糖(LPS)的方法制备COPD大鼠模型。建模后,治疗组灌胃给药,正常组及模型组灌胃等量生理盐水。评价肺功能,实时荧光定量PCR(Real-time PCR)检测肺组织中Smad3,Smad4,Smad6和Smad7mRNA表达,免疫组织化学检测大鼠肺组织中Smad3,Smad4,Smad6,Smad7蛋白表达。结果:与正常组比较,模型组用力肺活量(forced vital capacity,FVC),第1秒末时间肺活量(FEV_1)和FEV_1/FVC均显著降低(P<0.01);模型组肺组织Smad3和Smad4 mRNA的表达量升高(P<0.05),Smad6和Smad7 mRNA表达均降低(P<0.05);Smad3和Smad4蛋白的表达显著增强(P<0.01),Smad6和Smad7蛋白的表达显著减弱(P<0.01)。与模型组比较,二陈汤加味中、高剂量组FVC,FEV_1和FEV_1/FVC均显著提高(P<0.01);Smad3和Smad4 mRNA的表达量均下降(P<0.05),Smad6和Smad7 mRNA的表达量升高(P<0.05);Smad3,Smad4蛋白的表达显著减弱(P<0.01),Smad6,Smad7蛋白的表达显著增强(P<0.01)。结论:二陈汤加味能有效抑制细支气管结构重塑作用。其机制可能是通过降低Smad3,提高Smad6和Smad7,协调Smad4基因表达,抑制细支气管及肺组织结构重塑。 Objective: To observe the effects of Erchen Decoction on signal transducers Smads in lung tissue of chronic obstructive pulmonary disease (COPD) rats and to explore the mechanism of Erchen decoction on COPD. Methods: Fifty SD rats were randomly divided into 5 groups, 10 animals in each group, including normal group, model group and Erchen Decoction at low, medium and high doses (5, 10, 20 g · kg -1) · D ~ (-1)) group. The COPD rat model was made by the method of dripping smoked gas pipette and lipopolysaccharide (LPS). After modeling, the treatment group was intragastrically administered, and the normal group and model group were given the same amount of normal saline. Pulmonary function was assessed. The expression of Smad3, Smad4, Smad6 and Smad7 mRNA in lung tissue was detected by Real-time PCR. The expression of Smad3, Smad4, Smad6 and Smad7 in lung tissue was detected by immunohistochemistry. Results: Compared with the normal group, the forced vital capacity (FVC), FEV 1 and FEV 1 / FVC in the model group were significantly decreased (P <0.01). The levels of Smad3 and Smad4 mRNA in the model group The expression of Smad6 and Smad7 mRNA was significantly decreased (P <0.05), the expression of Smad3 and Smad4 protein was significantly increased (P <0.01), and the expressions of Smad6 and Smad7 protein were significantly decreased (P <0.01) . Compared with the model group, the FVC, FEV_1 and FEV_1 / FVC of Erchen decoction medium and high dose groups were significantly increased (P <0.01), the expression of Smad3 and Smad4 mRNA were decreased (P <0.05), Smad6 and Smad7 mRNA (P <0.05). The expressions of Smad3 and Smad4 were significantly decreased (P <0.01), and the expressions of Smad6 and Smad7 were significantly increased (P <0.01). Conclusion: Erchen Decoction can effectively restrain the remodeling of bronchiolar structure. Its mechanism may be through reducing Smad3, increasing Smad6 and Smad7, coordinating Smad4 gene expression, inhibiting bronchial and lung tissue remodeling.
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