基于NF-κB通路的支气管哮喘寒饮蕴肺证大鼠气道重塑机理及温阳化饮方干预机制研究

Recent studies have found that the nf-kappa B as a multidirectional adjustment role of nuclear in the airway by excessive activation of transcription factors, is the most closely watched in asthma pathogenesis of signal transduction system, one of the 1, 25 - (OH) 2 VD3 can inhibit the excessive activation of the nf-kappa B, thus inhibiting the lungs release of inflammatory factor, reduce airway inflammation, relieve airway remodeling.TCM holds that Yang deficiency drink stop, phlegm obstruction QiNi is the main pathogenesis of asthma.WEN YANG HUA YIN FANG may increase by 1, 25 - (OH) 2 VD3 body content or activity, inhibit the excessive activation of the nf-kappa B signaling pathways, thus affecting the airway remodeling.Guided by the overall concept, this study USES the method combining traditional Chinese and western medicine, copy the bronchus asthma rats models combined cold drink aggregates lung disease.Using Western blot method and fluorescence quantitative rt-pcr method to detect the nf-kappa B protein expression in lung tissue, and the I kappa alpha B mRNA expression predominate.Research on asthma cold drink aggregates lung airway remodeling mechanism.According to the principles of "syndrome differentiation" of traditional Chinese medicine, compare different from lung spleen kidney treatment curative effect, at the same time to clarify this change WEN YANG HUA YIN FANG on asthma cold drink aggregates lung airway remodeling of biological mechanisms, which will provide a scientific basis for clinical treatment of asthma.

近来研究发现NF-κB作为多向调节作用的核转录因子在气道中被过度活化，是哮喘发病机制中最受关注的信号转导系统之一，1,25-(OH)2-VD3能够抑制NF-κB的过度活化，从而抑制肺内炎性因子释放，减轻气道炎症，缓解气道重塑。中医认为阳虚饮停，痰阻气逆是哮喘发作的主要病机。温阳化饮方可能提高通过1,25-(OH)2-VD3体内的含量或活性，抑制NF-κB信号通路的过度活化，从而影响气道重塑。本研究以整体观念为指导，运用中西医结合方法，复制支气管哮喘寒饮蕴肺病证结合大鼠模型，运用Western blot法及荧光定量RT-PCR法检测肺组织中NF-κB的蛋白表达，以及IκBα的mRNA表达，研究哮喘寒饮蕴肺证气道重塑机制；依据中医"辨证论治"的原则，比较从肺脾肾论治的不同疗效，同时阐明温阳化饮方对哮喘寒饮蕴肺证影响气道重塑的生物学机制，为哮喘的临床治疗提供科学依据。

本课题探讨基于核转录因子NF-κB(nuclear factor-κB,NF-κB)通路，温阳化饮方干预支气管哮喘寒饮蕴肺证大鼠气道重塑的机制。采用卵蛋白致敏，加冰箱冷冻、冰水饲养、水中游泳等方法，建立支气管哮喘寒饮蕴肺病证结合大鼠模型，分别用1,25-(OH)2-VD3、小青龙汤、温阳化饮方和六君子汤进行干预，观察相关检测指标。结果显示造模成功，模型组大鼠的一般行为学表现与支气管哮喘寒饮蕴肺证的临床表现基本相符，微观指标的变化也证实了造模较为成功；而治疗组的四种药物对上述各项指标都有不同程度的改善，其中温阳化饮方疗效总体最佳。对于肺组织细胞核内NF-κB p65蛋白表达药物干预组大鼠明显低于模型组大鼠，相应的，药物干预组大鼠的肺组织细胞质内NF-κB p65蛋白表达明显高于模型组。提示对于支气管哮喘寒饮蕴肺证，温阳化饮方确有较好疗效，温阳化饮方疗效机制是通过改善大鼠血液中1,25-(OH)2-VD3的含量，调控肺组织NF-κB信号通路的基因表达，进而改善气道炎症和气道重塑。说明温阳化饮方的温补肺阳，温化寒饮及改善肺通气的作用的疗效机制，与其调控体内1,25-(OH)2-VD3的含量和肺组织NF-κB信号通路的基因表达有关。