血小板来源的生长因子受体识别肽在肝纤维化无创诊断中的应用

肝纤维化的早期诊断对于慢性肝病的诊治具有重要的意义，目前尚缺乏能区分各期肝纤维化的无创诊断方法。活化的肝星状细胞（HSC）是肝纤维化过程中纤维胶原的主要来源细胞，α-SMA被认为是活化HSC的标记物。在青年科学基金项目研究工作中，我们发现在纤维化的肝组织中，血小板来源生长因子受体-β（platelet derived growth factor receptor-β, PDGFR-β）分布的区域与α-SMA分布的区域在很大程度上相互重叠；更为重要的是，我们成功合成能特异识别PDGFR-β的pPB环肽，利用该环肽修饰脂质体后，能特异结合在活化的HSC上。因此，在本课题中，我们设想利用同位素标记的pPB环肽来显影纤维化肝组织中的PDGFR-β的表达情况，通过分子影像学的显影方法来诊断肝纤维化并尝试根据同位素结合量的差异区分不同程度的纤维化，从而为肝纤维化的无创诊断提供一种新方法。

It is critical for the diagnosis and management of chronic liver disease to diagnosis liver fibrosis as early as possible, but there is no effective noninvasive method to identify liver fibrosis at different stage at present. The key factors in hepatic fibrogenesis are the activation and proliferation of hepatic stellate cells (HSC). As a result of sustained or repeated liver injury, HSC undergo a process of activation and transform into myofibroblast-like cells, which are characterized by α-smooth muscle actin (α-SMA) expression. In our work supported by Grants from the National Nature Science Funds for Young Scholar, we found that most of the area positive for platelet derived growth factor receptor-β(PDGFR-β) was overlapped with the area positive for α-SMA. In addition, we prepared the pPB cyclic peptides which could specially recognize PDGFR-β. After the liposomes were modified with pPB, they could specially bind to activated HSC. Thus, in this study, we suppose to use radiolabeled pPB cyclic peptides to image hepatic PDGFR-β-expression in fibrotic livers in order to develop a noninvasive approach to diagnosis and stage liver fibrosis.