宿主信号分子BMP2通过细粒棘球蚴BMP/Smad信号通路调控虫体生长发育及其致病性的研究

包虫病是危害严重的人畜共患病，95%是细粒棘球蚴（Eg）感染所致囊型包虫病（CE），新疆是高发区。宿主信号分子BMP2调控Eg生长发育和致病性的研究未见报道。课题组前期研究发现活跃期CE病人病灶周围BMP2高表达，且BMP2促进体外Eg原头蚴向成囊方向发育；Eg自身存在BMP/Smad信号通路，提示BMP2可能通过BMP/Smad信号通路调控Eg生长发育及高致病性，但机制不明。本项目拟利用生发层原代细胞系，明确BMP2通过BMP/Smad信号通路对生发层原代细胞成囊发育的影响；其次Eg体外培养和体内接种动物方式，通过正向激活和反向干预方法，阐明BMP2调控Eg生长发育和致病性的分子机制，临床标本验证BMP2与Eg致病性的关系；最后使用BMP2中和抗体或抑制剂干预Eg感染的动物模型，探索用于CE治疗的可行性和有效性，对揭示Eg生长发育和致病机制、研制新型药物和开发新治疗方法具有重要科学意义。

Echinococcosis is a serious zoonoses in northwest of China and more than 95% cases are cytic echinococcosis (CE), which caused by Echinococcus granulosus (E. granulosus) infection. Xinjiang is a high risk epidemic region. Study on the effect of host signal molecule BMP2 on growth, development and pathogenicity of E. granulosus is rarely reported. In our previous study, we found that the high expression of BMP2 molecule was around lesions in CE patients with active stage; BMP2 promotes E. granulosus protoscolex development into cyst in vitro, and BMP/Smad signal pathway was in the presence of E. granulosus. It suggests that BMP2 may regulate the growth, development and high pathogenicity of E. granulosus through the BMP/Smad signaling pathway, but the mechanism is unknown. In this work, we plan to elucidate the effects of BMP2 on the encysted development of the primary cells of the germinal layer through the BMP/Smad signal pathway. Using human BMP2 stimulation and the inhibitor of BMPR I in E. granulosus cultivation system in vitro and in E. granulosus infection mice in vivo, we identify the molecular mechanism of E. granulosus growth, development and pathogenicity which was regulated by host BMP2, and verify the relationship between BMP2 and pathogenicity of E. granulosus by clinical specimens. Finally, we explore the feasibility and effectiveness for CE treatment by the use of BMP2 neutralizing antibody or inhibitor in the E. granulosus infected mice model in vivo. These studies have important scientific significance to reveal the mechanism of growth, development and pathogenicity of E. granulosus, and to develop new drugs and new therapeutic method.