HBeAgase与乙型肝炎核心抗原HBeAg的作用机制及其对肝细胞的保护

项目名称： HBeAgase与乙型肝炎核心抗原HBeAg的作用机制及其对肝细胞的保护

项目编号： No.31470036

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 赫荣乔

作者单位： 中国科学院生物物理研究所

项目金额： 90万元

中文摘要： 乙型肝炎严重危害我国人口健康，是我国最为重要的公共卫生问题之一。申请者发现，在口服蚓激酶胶囊（蚯蚓蛋白酶同功酶复合制剂）治疗脑血栓病人的过程中，其中具有肝炎核心e抗原阳性的病人，出现HBeAg转阴性或降低的现象。这一现象的发现，促使申请者从赤子爱胜蚓（Eisenia fetida）中分离出了一种同功酶，该酶能够识别和降解乙型肝炎核心e抗原，因此，申请者将其并命名为乙型肝炎核心e抗原酶HBeAgase。在此，本项目拟研究蚯蚓蛋白同功酶的结构与功能，包括与乙型肝炎核心e抗原的作用，HBeAgase在HBeAg上的作用位点。通过HepG2.2.15细胞系，同转基因小鼠、龙岩麻鸭等模式动物的研究，阐明HBeAg的降解与保护肝细胞之间的关系，包括HBeAgase在肠道吸收机制及在肝脏中的分布。从而进一步理解HBeAg在乙型肝炎中的作用，为研制以HBeAg作为潜在靶点的新药提供理论基础。

中文关键词： 蛋白质；作用机理；蛋白质降解；乙型肝炎；肝细胞保护

英文摘要： Hepatitis B is seriously harmful to the healthy of Chinese People, which is one of the most important problems for the public health. Recently, the applicants found that the HBeAg could be converted from positive to negative for the patients with cerebral infaction after taking capsule of earthworm lumbrokinase a group of earthworm proteases. This result is significant for us to carry out this project in which we have isolated an isozyme from the earthworm of Eisenia faetida. We called the isozyme HBeAgase because it can degrade HBeAg rapidly both in vivo and in vitro. Here, the applicants attempt to study the structure and function of HBeAgase and the effect on the molecule of HBeAg and identify the cleavage sits on HBeAg. Using HepG2.2.15 cell line, tansgenic mice and sheldrake, to explore the relationship between the degradation of HBeAg and liver protection, as well as the mechanism of this isozyme in the absorption through intestines and the distribution in liver. Our project will shed light on the further understanding the role of HBeAg in hepatitis and provide some important information to investigate new drug to regconize HBeAg as a potential target in the treatment of patient with hepatitis.

英文关键词： protein;mechanism;protein degradation;hepatitis;hepatocyte protection