Notch信号调控巨噬细胞极化参与泡球蚴感染肝纤维化的作用机制及干预研究

泡型包虫病（AE）是泡球蚴（Em）寄生肝脏所致“类肝癌样”致死性寄生虫病,Em在肝脏内长期寄生形成慢性炎症和肝纤维化，具体致病机制不清，阻碍包虫病的临床治疗进展。我们前期研究发现巨噬细胞极化参与Em持续性感染和肝损伤，Notch信号是调控巨噬细胞活化重要信号通路之一，可能通过调控巨噬细胞极化参与肝纤维化发生发展。在前期研究基础上本项目对泡型包虫病患者和不同感染时期泡球蚴感染小鼠模型进行肝脏病理特征、巨噬细胞极化类型、Notch信号相关分子等研究，探讨Notch信号和巨噬细胞在泡球蚴感染肝纤维化中的作用及机制；利用巨噬细胞特异性Notch信号敲除小鼠建立Em感染模型，分析Notch信号调控巨噬细胞极化参与肝纤维化进程的分子机制；通过向泡球蚴感染小鼠回输巨噬细胞，研究不同极化类型巨噬细胞对泡球蚴感染小鼠肝纤维化治疗作用及机制，为靶向干预巨噬细胞进行泡球蚴感染所致肝纤维化治疗提供新靶点和策略。

Alveolar Echinococcoisis is a lethal parasitic disease like hepatocarcinoma caused by Echinococcus. Echinococcus inhabits in live in the long-term and caused chronic inflammation and liver fibrosis gradually. However, the pathogenic mechanism is unclear. which hinders the progress of clinical treatment of hydatidosis. In our previous studies, we have found the macrophage polarization was involved in persistent infection and liver injury of Echinococcus multilocularis. Notch signaling pathway is one of the important signal pathways in regulating the activation of macrophages. Hence we speculate Notch signaling pathway could be participate in the process of hepatic fibrosis by regulating the polarization of macrophages. In order to find the key molecule of Notch signal pathway regulating macrophage polarization in the process of liver fibrosis, we would be analyze the relation between the liver pathological characteristics, the polarization types of macrophages and the related molecules of Notch signaling pathway to patients with hydatid echinococcosis and mice infected with Echinococcus multilocularis in different infection stages. Then, we will confirmed the molecular mechanisms and intervention of Notch signal pathway by observed the level of hepatic fibrosis of knockout macrophage-specific Notch mice and knockout macrophage-specific Notch mice injected macrophages of different polarization types.This study will provid a new target intervention to macrophages polarization for treatment hepatic fibrosis caused by Echinococcus multilocularis.