Clinical Efficacy Evaluation Of Yiqi Guben Capsule In The Treatment Of Childhood Asthma And Mechanism Of Regulating Mitochondria

1 Clinical efficacy evaluation of Yiqi Guben Capsule in the treatment of asthma in childrenObjective:To explore the clinical efficacy of Yiqi Guben Capsule in the treatment of asthma in children.Methods:A total of 100 children with asthma in remission stage（syndrome/pattern of lung and spleen qi deficiency）were randomly divided into TCM group and Western medicine group by random number table.TCM group was treated with Yiqi Guben Capsule and Western medicine group was treated with aerosol inhalation of budesonide suspension.After the course of treatment,the patients were followed up once at 3 months after treatment and 6months after treatment.The clinical efficacy was evaluated by evaluating the grade of asthma control level,the number of asthma attacks,the score of lung and spleen deficiency syndrome,the number of respiratory tract infections,and pulmonary function parameters in the two groups.Results:The total effective rate was 89.80%in the TCM group and 81.63%in the Western medicine group.The clinical efficacy of the TCM group was better than that of the Western medicine group（P<0.05）.Both the TCM group and the Western medicine group could effectively improve the asthma control level after treatment（P<0.05）,significantly reduce the lung and spleen qi deficiency syndrome score after treatment,and the TCM group had a better therapeutic effect on symptoms and signs such as fatigue,burnout,and anorexia compared with the Western medicine group（P<0.05）.The TCM group was also more effective than the Western medicine group in reducing the number of asthma attacks and respiratory tract infections（P<0.05）.In addition,FEV1%was significantly increased in the two groups after treatment,and the comparison between the groups revealed that the degree of improving pulmonary function in the TCM group was better than that in the control group（P<0.05）.Conclusion:Yiqi Guben Capsule has a definite clinical effect and can significantly improve the clinical control of asthma in children in remission stage,reduce the frequency of attacks,improve pulmonary function and relieve the symptoms of lung and spleen qi deficiency,especially in improving the symptoms and signs of fatigue,lassitude and anorexia in children.In addition,Yiqi Guben Capsule can enhance the body immunity of children and reduce the number of respiratory tract infections,and is safe without adverse reactions.2 Mechanism of Yiqi Guben Capsule in Improving Mitochondrial Dysfunction in Allergic Asthma MiceObjective:To explore the mechanism of Yiqi Guben Capsule in improving mitochondrial dysfunction in ovalbumin sensitized allergic asthma mice.Methods:Allergic asthma model was established by sensitization with OVA combined with aluminum hydroxide in mice.Hematoxylin-eosin staining was used to evaluate the infiltration of airway inflammatory cells in mice,Masson staining was used to evaluate the deposition of airway collagen in mice;transmission electron microscopy and flow cytometry were used to evaluate the effect of Yiqi Guben Capsule on mitochondrial function and mitochondrial biogenesis.RNA-seq transcriptome sequencing technology was used to analyze the biological processes and signaling pathways that may be enriched in Yiqi Guben Capsule and further clarify its mechanism of action in improving mitochondrial function.Results:The results of behavioral score,HE staining and Masson staining showed that the mice sensitized with OVA showed typical symptoms of asthma attack such as nodding respiration,dysphoria and abdominal spasm,and typical pathological changes of asthma such as massive inflammatory cell infiltration and collagen fiber thickening and deposition in lung tissue,suggesting that the model was successfully constructed.The symptoms of asthma attack,inflammatory cell infiltration and collagen fiber thickening in lung tissue were significantly alleviated after treatment with Yiqi Guben Capsule.Under transmission electron microscopy,mitochondrial swelling and ultrastructural damage in mouse lung tissue were significantly alleviated after Yiqi Guben Capsule intervention,mitochondrial cristae were more intact than before,and could significantly reduce ROS levels and mitochondrial membrane potential in mouse lung tissue,increase mitochondrial number in lung tissue,thereby improving mitochondrial dysfunction and alleviating oxidative stress injury;and by up-regulating the m RNA and protein expression levels of PGC-1αand TFAM,the main regulators of mitochondrial biogenesis,and then increasing mt DNA copy number,it effectively promoted the recovery of mitochondrial function and enhanced mitochondrial biogenesis.Transcriptome sequencing analysis showed that 216 genes were significantly up-regulated and 119 genes were significantly down-regulated after treatment with Yiqi Guben Capsule,and differential genes were mainly enriched in extracellular regions,extracellular matrix and other items,involved in biological processes such as inflammatory response and cell adhesion,and played a therapeutic role through signaling pathways related to immunity and inflammation.Conclusion:Yiqi Guben Capsule can improve mitochondrial function,promote mitochondrial biogenesis and alleviate oxidative stress injury by regulating mitochondrial structure,number,membrane potential changes and ROS generation,thereby reducing airway inflammation in asthma.3 Yiqi Guben Capsule Regulates PI3K/AKT/PGC-1αSignaling Pathway to Reduce Airway Inflammation in Allergic AsthmaObjective:To investigate the potential therapeutic mechanism of Yiqi Guben capsule on airway inflammation in asthmatic mice based on transcriptomic sequencing results.Methods:Allergic asthma model was induced by OVA combined with AL（OH）₃sensitization in mice.Yiqi Guben Capsule,PI3K inhibitor LY294002,Yiqi Guben Capsule combined with LY294002 and Yiqi Guben Capsule combined with PI3K agonist 740Y-P were used to evaluate the model construction by airway reactivity test,HE staining and PAS staining.The contents of OVA-s Ig E,INF-γ,IL4,IL5 and IL13 in BALF were detected by ELISA.The m RNA and protein expressions of key factors on PI3K/AKT/PGC-1αsignaling pathway in lung tissues were detected by q RT-PCR and Western blot.Results:The results of behavioral score,HE staining and PAS staining showed that OVA-sensitized mice showed typical symptoms of asthma attack such as nodding respiration,dysphoria and abdominal spasm,a large number of typical pathological changes of asthma such as inflammatory cell infiltration and goblet cell hyperplasia in lung tissue,airway resistance was significantly increased,and OVA-s Ig E expression in BALF was up-regulated,suggesting that the model was successfully constructed.After intervention with Yiqi Guben Capsule or LY294002,the symptoms of asthma attack,inflammatory cell infiltration in lung tissue and goblet cell proliferation in mice were significantly alleviated,airway resistance and Th2 cytokine expression level in lung tissue were significantly reduced,the m RNA expression and phosphorylation levels of PI3K and AKT were significantly reduced,and the m RNA and protein expression of PGC-1αand TFAM,key factors regulating mitochondrial biogenesis,were significantly increased;and the effect of Yiqi Guben Capsule combined with LY294002 in promoting mitochondrial biogenesis and relieving chronic airway inflammation was significantly better than that of the two alone,and 740Y-P significantly attenuated the effect of Yiqi Guben Capsule on improving mitochondrial function and relieving chronic airway inflammation in asthmatic mice.Conclusion:Yiqi Guben Capsule improves mitochondrial function and promotes mitochondrial biogenesis by regulating PI3K/AKT/PGC-1αsignaling pathway,thereby reducing airway inflammation in asthma.