从SIRT3介导的线粒体动力学探讨固本防哮饮防治儿童哮喘的作用机制

哮喘患儿常表现为可逆的阻塞性通气功能障碍，新近研究表明线粒体相关基因的异常表达与肺功能下降密切相关，提示线粒体功能损伤是肺功能降低的重要原因。SIRT3能够通过乙酰化网络影响线粒体动力学，而线粒体动力学是影响线粒体功能的重要因素，因此线粒体动力学可能是深入研究中医药改善哮喘患儿肺功能的新方向。固本防哮饮是全国名老中医江育仁教授经验方，前期研究发现它能明显改善哮喘患儿及模型小鼠肺功能；增加线粒体呼吸链复合物转录水平、减少ROS产生；降低影响SIRT3活性的4-HNE、MDA的表达。另外蛋白质组学结果提示该方可能对SIRT信号通路有调控作用。据此提出假说：固本防哮饮可能通过SIRT3介导的线粒体动力学影响线粒体功能，从而改善肺功能、缓解气道炎症及重塑，达到防治哮喘的目的。本课题拟采用细胞转染、siRNA干扰、透射电镜等技术，从SIRT3信号通路及线粒体动力学探讨固本防哮饮防治哮喘的作用机制。

Children with asthma often show reversible obstructive ventilation dysfunction. A recent study showed abnormal expression of mitochondrial-related genes was closely related to impaired lung function, suggesting mitochondrial function damage was an important cause of reduced lung function. SIRT3 could affect mitochondrial dynamics through acetylation networks, and mitochondrial dynamics is an important factor affecting mitochondrial function. Therefore, in-depth study of mitochondrial dynamics may be a new direction to improve lung function in children with asthma by TCM. Gubenfangxiao decoction (GBFXD) is an empirical formula prescribed by Professor Jiang Yuren, a prestigious TCM pediatrician in China. Previous study demonstrated that GBFXD could significantly improve lung function of children or mice with asthma, increase the transcription level of mitochondrial respiratory chain complex, reduce ROS and the expression of 4-HNE and MDA which could activate SIRT3. In addition, the results of proteomics suggested GBFXD could regulate signal pathway of SIRT. In summary,we hypothesize that GBFXD could prevent and treat asthma by SIRT3 mediated mitochondrial dynamics, which could improve lung function, alleviate airway inflammation and remodeling. In this study, cell transfection, siRNA interference and transmission electron microscopy will be used to explore the mechanism of GBFXD in prevention and treatment of asthma through mitochondrial dynamics meditated by SIRT3 signal pathway.