A Study On Interventional Mechanism Of Yang-warming And Fluid-dispersing Formula Regulating HIF-1α Pathways To Intervene Autophagy Of Asthma Rats With Syndrome Of Cold Fluid Accumulation In Lung In Terms Of Phlegm-fluid Retention Theory

Objective: Through the analysis of etiology of phlegm and fluid retention and pathogenic mechanism of the rat model of bronchial asthma with syndrome of cold retention accumulation in lung and the application of Yang-Warming and Fluid-Dispersing Formula for intervention treatment,we explored the effect of autophagy in lung tissue on phlegm and fluid retention and hypoxia,and its significance in the pathogenesis of asthma with the syndrome of cold retention accumulation in lung,aiming to explore the therapeutic effect and intervention mechanism of TCM on airway inflammation of bronchial asthma.Methods: Both TCM theoretical study and molding method of modern medicine were employed in the study.We summarized the theory about phlegm and fluid retention from classic TCM literature,and discussed the etiology and pathogenesis of phlegm and fluid retention and its relationship with related viscera,hypoxia and autophagy to clarify its pathogenesis and enrich TCM theory.In experimental study,we established the rat model of bronchial asthma with syndrome of cold retention accumulation in lung by egg ovalbumin sensitization,ice-water mixture,cold stimulation,and used Yang-Warming and Fluid-Dispersing Formula for drug intervention to clarify the mechanism of Chinese herbal compound intervention on autophagy of asthma cells of bronchial asthma with syndrome of cold retention accumulation in lung.Results: We successfully established the rat model of bronchial asthma with syndrome of cold retention accumulation in lung,explored the key role of phlegm and fluid retention in the disease onset of the rat model and the correlation between hypoxia and autophagy.Drug intervention showed that compared with model group there were significant differences in HE staining,Masson staining,PAS staining and ELISA inflammation factor expression for groups of Yang-Warming and Fluid-Dispersing Formula,Xiaoqinglong decoction,Liujunzi decoction,Rapamycin.Transmission electron microscope,PCR,Western blot and immunohistochemistry also indicated the five sets of drugs all have different degree of improvement in such autophagy genes as mTOR,LC3,Beclin1 and ATG5.Pathomorphology and Molecular biology detection showed that Yang-Warming and Fluid-Dispersing Formula has the most obvious effect.Conclusion: Our research showed that Yang-Warming and Fluid-Dispersing Formula can promote the autophagy of lung tissue in rats with syndrome of cold retention accumulation in lung and relieve airway inflammation.The mechanism may be that by inhibiting the expression of HIF-1α pathway,Yang-Warming and Fluid-Dispersing Formula improves oxygen levels in body,reduces cell damage,strengthens transformative function of Qi,enhances the level of cell autophagy to remove phlegm and fluid retention and other metabolic waste products in the body,reduces airway inflammation so as to alleviate asthma.Xiaoqinglong decoction,Liujunzi decoction,Rapamycin can promote the autophagy of lung tissue in rats with syndrome of cold retention accumulation in lung and alleviate airway inflammation,but the effect is not as good as Yang-Warming and Fluid-Dispersing Formula.