长链非编码RNA-GDNFOS1介导枳术通便汤促慢传输型便秘肠壁神经丛修复机制的研究

项目名称： 长链非编码RNA-GDNFOS1介导枳术通便汤促慢传输型便秘肠壁神经丛修复机制的研究

项目编号： No.81473506

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： 范一宏

作者单位： 浙江中医药大学

项目金额： 74万元

中文摘要： 结肠肌间神经丛退行性改变是慢传输型便秘（STC）发病的基本病理基础，外源性GDNF能通过促进肠神经元修复起到改善STC结肠动力的目的，但目前外源性GDNF临床应用尚存不可逾越的限制。我们前期研究发现：枳术通便汤有类外源性GDNF作用，但具体机制有待进一步阐明。文献报道GDNF互补链上存在着一长链非编码RNA（lncRNA）GDNFOS1，我们前期生物信息学分析证实该lncRNA与GDNF间存在很强的调控相关性。据此提出GDNFOS1可通过调节GDNF的表达，修复STC肠壁超微结构；枳术通便汤可通过靶向干预GDNFOS1从而起到类外源性GDNF作用的假说。本项目拟采用中药血清药理学、神经药理学等手段，在整体（动物模型、患者）、细胞（体外培养肠胶质细胞）及分子水平阐明GDNFOS1调控GDNF表达水平的作用机制及枳术通便汤对GDNFOS1的表达调控作用，为中医药治疗STC提供新靶点和理论基础。

中文关键词： 长链非编码RNA；枳术通便汤；慢传输型便秘；肠神经系统

英文摘要： The pathological basis of the aggravating development of slow transit constipation (STC) is the degenerative change of the colonic myenteric plexus. Exogenous GDNF can improve the STC colonic motivity through promoting the repair of intestinal neuron. However，the clinical application of exogenous GDNF is still under impassible restrictions up to now. We found in previous research that ZhizhuTongbian Decoction had similar effect as GDNF，though the mechanism needed to be studied. Some literature reports that there exists a long non-coding RNA (lncRNA) named GDNFOS1 in the complementary chain of GDNF. Through bioinformatics analysis，we have confirmed that there is strong correlation between lncRNA and GDNF. Therefore，we suppose that GDNFOS1 can repair the ultrastructure of STC intestinal wall by regulating the expression of GDNF. It is also supposed that ZhizhuTongbian Decoction，which takes a role as exogenous GDNF，can interfere GDNFOS1. By means of serum pharmacology of traditional chinese medicine and neuropharmacology，the project aim to elaborate the regulative mechanism of to the expression of GDNF by GDNFOS1，and the regulative effect of ZhizhuTongbian Decoction on the expression of GDNFOS1. The study will be carried out on the levels of whole (animal model and patients)，cell (enteric glial cells cultured in vitro) and molecular biology. The research may provide new insight towards the TCM therapy of STC.

英文关键词： lncRNA;Zhizhu Tongbian Decoction;Slow Transit Constipation;enteric nervous system