细粒棘球蚴GLUT摄取宿主葡萄糖的调控机制及其抗包虫药物靶点研究

细粒棘球蚴（Eg）感染所致囊型包虫病（CE），危害严重，亟需新药物。阻抑Eg摄取中间宿主体内葡萄糖，是研发抗包虫药物的思路之一，然而Eg摄取宿主葡萄糖的机制未知。我们前期在Eg中发现了葡萄糖转运蛋白（GLUT）和胰岛素受体（IR）信号通路，及其抑制剂能高效抑制Eg幼虫的活性。为阐明EgGLUT摄取宿主葡萄糖的作用及其调控机制，对致病性的影响和鉴定药物靶点。本课题拟通过激光共聚焦等实验，鉴定EgGLUT的表达、定位、葡萄糖摄取和转位等；体内外实验，分别通过正反向干预EgIR、EgAMPK和EgGLUT等，确定EgGLUT的调控机制及其对葡萄糖摄取、Eg幼虫活性和致病性的影响；GLUT抑制剂的体内外抗包虫药效实验，鉴定药靶；CE患者标本中分析EgGLUT功能与CE（活跃、非活跃）的相关性。本课题是阐明Eg幼虫摄取葡萄糖的调控机制，鉴定抗包虫药物靶点的重要组成部分，为研发新型抗包虫药物奠定基础。

Cystic echinococcosis (CE) is one of the neglected and life-threatening zoonoses, which is caused by the larval stage of Echinococcus granulosus (Eg). It’s urgent to develop novel drug targets for the helminth. Block of glucose uptake from the intermediate host is a way to develop the anti-echinococcosis drug target. However, its mechanism is still unknown. We found that E. granulosus insulin receptor signaling pathway could influence the quantity of glucose in the larvae of E. granulosus and is an important anti-echinococcosis drug target. And glucose transport protein (GLUT) inhibitor could reduce the viability of larvae of E. granulosus. As glucose in the E. granulosus was transported from the environment of intermediate host. It’s suggested that EgGLUT might control the glucose uptake from the intermediate host and is an important anti-echinococcosis drug target. In this work, we plan to clone the gene sequence of EgGLUT, prepare the antibody of EgGLUT, and detect the expression, location, glucose uptake function and translocation of EgGLUT by the confocal laser scanning microscope and other molecular biology technology. Then we would identify the effects of Eg insulin receptor signaling pathway and EgAMPK signaling pathway on the glucose uptake of EgGLUT, viability of larvae and pathogenicity, by treated with insulin or AICAR(AMPK agonist) and inhibitors (EgIR signaling pathway, EgAMPK signaling pathway and EgGLUT), in vitro and in vivo. The curative effect and safety of EgGLUT inhibitor would be evaluated, in vitro and in vivo. Furthermore, the relationship between the EgGLUT function and different type of CE (active and inactive) was analyzed, in the specimen of CE patient. This study would lay a basis for further research on the mechanism of glucose uptake in E. granulosus, and provides a theoretical proof for clinical treatment of hydatid disease.