基于血流量和氧代谢的肝硬化病人脑功能网络改变的机制研究

项目名称： 基于血流量和氧代谢的肝硬化病人脑功能网络改变的机制研究

项目编号： No.81471644

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： 郑罡

作者单位： 中国人民解放军东部战区总医院

项目金额： 73万元

中文摘要： 肝性脑病是由氨和锰等神经毒素引起的代谢性脑疾病。依据氨和神经炎症共同作用导致肝性脑病理论，以及氨和锰在肝性脑病中的相互作用，本研究推断氨、锰及神经炎症在肝性脑病的脑功能改变中可能存在共同作用机制。为了直接地反映动态和静态脑功能，本项目具体内容如下：1）基于动脉自旋标记技术，拟构建动态和静态脑血流及氧代谢功能网络，以反映肝硬化病人的灌注及代谢脑功能网络的同步性和一致性特征；2）拟基于图论分析对脑网络进行局部和全局量化，研究肝硬化病人的灌注及代谢脑网络量化改变与氨、锰和促炎因子间的机制；3）拟通过锰调制的大鼠肝硬化模型，进一步补充研究神经毒素、神经炎症及脑功能改变间的机制。因为灌注网络改变与神经毒素递送引起的脑功能改变有关，而氧代谢网络改变可能与神经炎症导致的脑功能异常有关，所以本研究有可能为肝硬化病人早期脑功能改变提供新量化指标。

中文关键词： 肝硬化；脑功能网络；血流量；氧代谢

英文摘要： Hepatic encephalopathy (HE) is a metabolic brain disease caused by neurotoxins such as ammonia and manganese. Currently, hyperammonaemia and neuro-inflammation are thought to have synergistic roles in inducing neurological alterations in HE. Moreover, there existes a synergistic effect between manganese and ammonia. In this proposal, our hypothesis is that ammonia, manganese and neuro-inflammation could have synergistic roles in HE. Based on the arterial spin labeling MRI, we will construct both dynamic and static networks for cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2). Firstly, perfusion and metablic functional connectivity will be quantified to local and global properities of networks based on graph analysis. Secondely, relationships between changes in network properities, ammonia, manganese and pro-inflammatory cytokines will be calculated to show their mechanisms in HE. Thirdly, experiments among cirrhotic rats exposed by manganese will be performed to verify these findings. Changes in CBF networks could be related with brain dysfunctions caused by neurotoxins delivery. Altered CMRO2 networks might be corresponding to impaired brain functions induced by inflammation. Our results could provide new quantified features for the early diagnosis of HE.

英文关键词： cirrhosis;brain functional network;cerebral blood flow;cerebral metabolic rate of oxygen