项目名称： Wnt7a调节腭帆提肌扩增规律的实验研究

项目编号： No.81470729

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 石冰

作者单位： 四川大学

项目金额： 73万元

中文摘要： 目前的腭裂整复技术虽然较前已有明显改进，但仍存在10-20%腭裂患者术后腭咽闭合不全，严重影响了患者的生存质量。究其原因，我们发现软腭长度和体积的不足是最主要的影响因素。因此，利用生物学手段增加软腭长度和体积，尤其是腭帆提肌的组织量，将是改进腭裂患者术后腭咽闭合的新途径。近年来研究发现Wnt信号通路在腭裂的发生中起着重要作用，已成为腭裂发病机制中的研究热点，同时，Wnt家族之一的Wnt7a作为实验治疗肌肉营养和发育不足的潜在效果最佳。为此，本课题拟通过将不同浓度的Wnt7a作用于在体的大鼠腭帆提肌和体外培养的腭裂患者的腭帆提肌细胞，在连续时间点，应用分子生物学、肌电实验等技术，从器官、细胞、分子层面体内体外多角度来研究Wnt7a调节腭帆提肌扩增的规律，并摸索其与其他生长因子协同或拮抗剂联合使用时腭帆提肌的扩增规律，阐明Wnt7a扩增腭帆提肌的机制和技术标准，为开展腭裂治疗新方法奠定基础。

中文关键词： 腭帆提肌；扩增；腭裂；非经典Wnt信号通路；Wnt7a

英文摘要： Though the surgical technique of palatoplasty has greatly improved, velopharyngeal insufficiency (VPI) remains a tough post-operative complication to 10-20% patients, whose living standard is largely impaired. Inadequate length of the soft palate and a lack of muscle mass constitute the main cause for the defiency. Thus, to enhance the length and volume of the soft palate muscle, especially the levator veli palatini(LVP), via methods in molecular biology, might be a promising approach to ameliorating VPI after palatoplasty. Recent years has seen intensive researches on Wnt signaling pathway, which has become a hotspot in the pathogenesis of cleft palate. Meanwhile, Wnt7a, a member of the Wnt family, proves to be a promising candidate for development as an ameliorative treatment for muscular astrophy. Our study aims to explore the regular pattern Wnt7a might have in dealing with LVP, and the potential interaction Wnt7a might have with other factors known to promote or inhibit muscle growth. Myoblast primary culture, electromyography and methods in molecular biology are applied to examine the effect of Wnt7a, with different dose and action time, has on the LVP muscle from an organic, cellular, and molecular angle. The study may serve as an early stage of feasibility study of clinical use, and is likely to provide fundamental support for a brand new therapy for the combined and sequencial treatment of cleft palate.

英文关键词： levator veli palatini;amplification;cleft palate;noncanonical Wnt pathway;Wnt7a