肝郁证的影像遗传学与基因调控网络研究

项目名称： 肝郁证的影像遗传学与基因调控网络研究

项目编号： No.81230085

项目类型： 重点项目

立项/批准年度： 2013

项目学科： 医药、卫生

项目作者： 吕志平

作者单位： 南方医科大学

项目金额： 280万元

中文摘要： 肝郁证与肝主疏泄功能密切相关，疏泄失常表现为肝气逆与肝气郁。我们前期的研究发现肝郁证的发病与脑中枢有关，我们拟采用脑部BOLD-fMRI成像技术，对正常志愿者和肝郁患者进行不同脑区功能变化定位研究，以确定肝郁证的功能改变脑区。通过外显子测序和高通量HiSeq测序发现肝郁患者的易感基因，MicroRNA测序发现患者血清中相关的miRNA,电化学法和液相蛋白芯片技术发现脑脊液神经内分泌变化。然后通过猕猴和小鼠肝郁模型及关键基因敲除和过表达小鼠两类模型来验证通过患者研究得出的结论，采用BOLD-fMRI成像和脑定位仪来验证功能改变脑区，HE、尼氏染色观察脑组织形态改变，采用免疫组化、免疫印迹和PCR技术来检测易感基因的表达变化，最终找到肝郁证与影像遗传学及基因调控网络的关系。

中文关键词： 肝郁证;影像遗传学;基因调控网络

英文摘要： Syndrome of Gan stagnation is closely related to liver's function of controlling dispersion .If it had functional disorder,the liver would performed for Liver-qi Invasion Syndrome and liver Qi stagnation. Our previous study found that gan stagnation is related to the Brain central nervous system. We will adopt BOLD-fMRI techniques to study the changes of different brain regions of normal volunteers and patients of stagnation in order to determine the location of brain area whose function changed. Through exon sequencing and high-throughput HiSeq sequencing revealed the predisposing genes of patients who have gan stagnation , Through MicroRNA sequencing found related miRNA in the patients'serum.Use electrochemical method and liquid phase protein chip technology to test CSF in order to find neuroendocrine changes. Then through the Macaque and mouse model and key gene knockout and overexpression in mice two models to verify the conclusion we study by patients, using BOLD-fMRI tecnology and cerebral localization instrument to verify the function change of brain areas.Adopt HE,Nissl staining methods to observe Histological changes of brain, using Immunohistochemistry, Western blotting and PCR technology to test expression changes of susceptibility gene .Eventually we could find out the relationship between gan stagnation and imaging genetics , gene regulatory net.

英文关键词： gan stagnation;imaging genetic;gene regulation net