调控日本血吸虫感染小鼠MHCⅡ+/-肝星状细胞分化的机制：吡喹酮的作用

血吸虫病仍是危害健康的重要寄生虫病，肝纤维化为主要病理基础。因杀虫后肝纤维化仍可持续发展，临床上缺乏有效应对措施，成为影响血防工作质量的关键问题。肝星状细胞（HSCs）受炎性刺激后活化、转化并分泌细胞外基质，是肝纤维化发生、发展的中心环节，TGF-β和IFN-γ是关键参与因素。基于前期研究，发现血吸虫感染鼠活化HSCs呈现MHC Ⅱ+/MHC Ⅱ-亚群分化，不同亚群细胞各具不同优势功能，且吡喹酮对两群细胞效应不同，并结合HSCs研究进展，提出"血吸虫感染后，肝脏局部微环境中TGF-β/IFN-γ交互作用，影响HSCs活化和MHC Ⅱ+/MHC Ⅱ-功能群分化方向；吡喹酮可能通过特定miRNAs干预活化MHC Ⅱ-HSCs的TGF-β/Smad信号通路，抑制TGF-β的功能，发挥抗肝纤维化作用"的研究假设。验证该假设，将为深入阐明血吸虫病肝纤维化及吡喹酮抗血吸虫病肝纤维化机制，提供试验基础。

At present, schistosomiasis japonica is still an important parasitic disease in China, the hepatic fibrosis is the main pathological basis of the disease. Because hepatic fibrosis remains development even after chemotherapy targeting elimination of adult worms, it become one of the key problems hindering the control of schistisomiasis.It is known that the production and deposition of extracellular matrix by hepatic stellate cells(HSCs)following activation plays a key roles in hepatic fibrosis, and the process involve mainly in regulation of TGF-βand IFN-γ. Our previous studies revealed that schistosome infection activated HSCs could be differentiated into MHC Ⅱ+ and MHC Ⅱ-subpopulations,each had its own dominant functions and especially, praziquantel exerts different influences on them. Based on former studies, we hypothizes that: on schistosome infection,the interaction of TGF-β/IFN-γ in hepatic microenviroment may affect the differentiation of MHC Ⅱ+/MHC Ⅱ-HSCs. Praziquantel may play anti-fibrotic roles by interfering with TGF-β/Smad signal pathway of HSCs through specific miRNAs and thereafter inhibiting funtionally TGF-β. The aims of this study focus on further demonstrating the mechanisms of hepatic fibrosis caused by schistosomiasis and anti-fibrotic effects of praziquantel.