血吸虫病是严重危害人类健康的重大寄生虫病。血吸虫虫卵引起的肝脏肉芽肿和纤维化病变是导致晚期血吸虫病及死亡的主要原因，但目前血吸虫性肝病发生的细胞和分子机制仍未阐明。研究表明miRNA在包括传染病在内的多种人类疾病的发生发展中发挥重要的调控作用，申请人前期研究已鉴定了血吸虫性肝病相关的宿主miRNAs, 其中一些miRNAs在该病进程中已显示有重要功能。本课题将以日本血吸虫病小鼠为动物模型，以8型腺相关病毒为载体，通过转染干预实验以上调或下调目标miRNA的表达，并观察小鼠疾病表型变化，从而鉴定具有致病相关功能的miRNA分子，并确定其在肝脏不同类型细胞中分布及表达丰度；通过体内、外动物及多种细胞模型实验，分析功能miRNA的靶基因及其信号通路和分子机制；本课题预期结果不仅能阐明宿主miRNA在血吸虫致病中的调控作用及其机制，而且为治疗血吸虫性肝纤维化提供新的思路和干预措施。

Schistosomiasis remains a major public health problem worldwide. The primary cause of death from schisitosomisis is formation of egg-inducing granuloma and liver fibrosis, but the exact cellular and melocular mechanism of hepatic schsistomiasis is still largely unkcnown. Recent investigations indicated that dysregulation of microRNAs was observed in various diseases including infectious diseases, but the role of miRNA in schsitosomiasis has not been reported. In this study, we will identify miRNAs which are specifically regulated in the liver of mouse model infected with Schistosoma japonica by performing microarray analysis and northern blot etc. We will further find the miRNAs which play an important role in the pathogenic processes of hepatic schistosomiasis through intervention using gene transferring of recombinant adeno-associated virus (rAAV8) that give either over-expression or knockdown of the target miRNAs. Potential mechanism of their roles in the hepatic schistosomiasis will be investigated by indentifying their target cell, target genes and involved signalings. This study will demonstrate the roles of miRNA in schistosome liver fibrosis and provide a potential novel approach using the miRNA-mediated therapeutics in treatment of schistosomiasis.