中文摘要
血吸虫病仍然是我国公共卫生领域的重大传染病,慢性或反复感染导致肝纤维化是临床亟待解决的重要问题,其机理尚未明确。申请者在国家自然科学青年基金资助下,发现在小柴胡汤抑制小鼠血吸虫肝纤维化进程中,热休克蛋白47(HSP47)表达下调。已有研究证实,HSP47是胶原特异性分子伴侣,其主要来源于肝星状细胞的活化,在血吸虫肝纤维化进程中,与TGF-β、CDGF共同发挥作用。动物实验表明,干扰HSP47表达可降低胶原合成。因此我们推测,小柴胡汤可能通过干预HSP47表达,从而调控TGF-β/ Smad信号通路,实现抗肝纤维化。本项目设计HSP47小干扰RNA,体外与体内转染考察HSP47表达与肝纤维化、TGF-β/ Smad信号通路以及小柴胡汤作用之间的关系,从分子、细胞、组织、动物整体水平,阐明小柴胡汤抗纤保肝机制,并为临床应用提供理论基础。研究小柴胡汤干预血吸虫肝纤维化的机制,国内外鲜有报道。
英文摘要
Schistosomiasis is a major infectious disease of public health in our country. Chronic patients with liver injury and even failure is an important problem needed to be solved, the liver fibrosis is the main pathological features and the mechanism is not yet clear. The application of Xiaochaihu decoction can inhibit liver fibrosis of Schistosomiasis. Supported by NSFC funding, we found that HSP47 proteion has decreased in the process of schistosomiasis liver fibrosis after treated with Xiaochaihu decoction. Studies showed that heat shock protein 47 (HSP47) is a collagen specific molecular chaperone, played a key role with TGF beta, CDGF in schistosomiasis liver fibrosis. animal experiments showed that, collagen synthesis could be decreased after the interference of HSP47. We concluded that the function of anti-hepatic fibrosis with Xiaochaihu Decoction may interfere with the regulation of HSP47 and TGF- beta / Smad signal pathway. We design HSP47 small interfering RNA, the relationship between the expression of HSP47 and hepatic fibrosis, TGF beta / Smad signal pathway and Xiaochaihu decoction treatment will to be investigated in vitro and in vivo transfection experiment. And the anti-fibrosis and hepato-protective mechanism of Xiaochaihu decoction will be explored in the level of molecule, cell, tissue and animal. The study could provide a theoretical basis in clinical application for Xiaochaihu decoction on liver fibrosis. There is no report on the mechanism of Xiaochaihu decoction in schistosomiasis treatment.
