无创诊断非酒精性脂肪性肝炎及评估其预后的靶向分子影像学研究

It is crucial for the management of nonalcoholic fatty liver disease (NAFLD) to early and accurately diagnose nonalcoholic steatohepatitis (NASH). However, there is no promoted, non-invasive and accurate method to diagnose NASH in clinics. In our previous study, it has been found that there is significantly increased expression of integrin alphavbeta3 receptor in liver with NASH compared to normal liver and liver with simple steatosis. In this study, we will further assess the association between hepatic expression of integrin alphavbeta3 receptor and the severity of liver disease in NAFLD, and identify the major cells expressing this receptor in liver with NAFLD. Then, the cyclic RGD peptide ligand fragment, which binds specifically to this receptor, will be prepared and labeled with gadolinium to be a tracer for MRI molecular imaging the expression of integrin alphavbeta3 receptor in liver with NAFLD. The expression difference of integrin alphavbeta3 receptor in the images will be compared in order to identify NASH and assesse the prognosis of liver disease. The study will provide an non-invasive and accurate method for the extensive screening, timely diagnosis and curative effect observation of NASH, which will benefit an increasing number of patients with NAFLD.

尽早地、准确地识别非酒精性脂肪性肝炎（NASH）对于非酒精性脂肪性肝病（NAFLD）的防治有重要的意义，但是目前临床上缺乏可推广运用、无创伤性、能准确识别NASH的诊断方法。本课题组前期研究发现，与正常肝组织和单纯肝脏脂肪变性的肝组织相比，出现NASH病理表现的肝组织有着更显著的整合素alphavbeta3受体的表达。在本项目中，本课题组将进一步研究NAFLD的肝组织中整合素alphavbeta3受体的表达水平与肝病严重程度的相关性，并识别肝组织中表达该受体的主要细胞；随后构建钆标记的靶向于该整合素受体的RGD环肽配体片段作为影像示踪剂，利用MRI分子影像学方法来显影肝组织中该整合素受体的表达，通过比较图像中该整合素受体的表达差异，从而识别NASH并评估肝病的预后。本课题的实施将可能为NASH的大规模筛查、及时诊断和疗效观察等提供一种无创伤性的诊断方法，从而造福于日益增多的NAFLD患者。