SjCa8在日本血吸虫尾蚴侵入宿主过程中作用的分子机制研究

项目名称： SjCa8在日本血吸虫尾蚴侵入宿主过程中作用的分子机制研究

项目编号： No.30800966

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 吕志跃

作者单位： 中山大学

项目金额： 20万元

中文摘要： 尾蚴侵入机体的过程及其机制是血吸虫病防治研究的基础和热点。申请者通过对血吸虫8kD钙结合蛋白SjCa8的研究发现，SjCa8只在血吸虫尾蚴和皮肤期童虫中特异性短程表达，且只分布于体膜、头腺、钻腺及分泌物中，并与腺体中富含的钙离子和蛋白水解酶重叠分布。体外实验显示：SjCa8能明显抑制巨噬细胞NO的生成。提示SjCa8可能与尾蚴腺体中蛋白水解酶的分泌和活性、虫体破损体膜的修复及童虫对宿主免疫调控等有关，推测SjCa8是尾蚴入侵宿主过程中的一个关键分子。为此，本项目拟进一步采用RNAi、酵母双杂交、双荧光标记等技术，系统研究SjCa8对尾蚴腺体蛋白水解酶分泌与活性的影响、SjCa8维持尾蚴体膜完整性及钙离子动态变化中的作用、以及SjCa8在皮肤期童虫逃避宿主免疫清除中作用的分子机理，深入阐明SjCa8在尾蚴侵入宿主过程中的作用及其机制，为评价SjCa8作为血吸虫病疫苗或药物新靶标提供科学依据。

中文关键词： SjCa8;日本血吸虫；尾蚴；侵入；分子机制

英文摘要： Thus far, the mechanisms by which free-living cercariae locate and penetrate definitive host skin or host response to the parasites remain unanswered.Understanding the mode of larval invasion and, in parallel, the mechanism of immune evasion utilized by invading larvae is vital to rational development of vaccines or drugs to prevent this disease.RT-PCR and Western-blot revealed SjCa8 can be detected in cercaria and skin-stage schistosomulum but not lung-stage schistosomulum, adult or egg and was localized to head gland, penetration gland tubes and penetration glands where Ca2+ was abundant, and the cercarial tegument (but not tegument of tail) and body-tail junction. Furthermore, SjCa8 was interestingly detected in cerarial secretions. The characterization of SjCa8 indicated it may undergo structural and physiological modifications, including repair of the surface membrane, changes in permeability that account for the loss of water tolerance, activities of calcium-depending enzymes, and immune signaling, etc. To get more information of SjCa8 involed in host invasion,RNAi, yeast two-hybrid system and double labeled fluorescence detection will be performed in this project.

英文关键词： SjCa8;Schistosoma japonicum;cercaria;invasion; molecular mechanism