中文摘要
慢乙肝肝纤维化(HF)程度与外周血纤维化蛋白(FBRS)和Th17正相关。Th17分泌IL-17A和FBRS通过MAPK信号分别上调HSC表达TGFβ受体和TGFβ1而致其激活。养阴活血组方的柔肝方是治疗乙肝HF有效验方,其可抑制HSC活化,降低Th17及FBRS表达。提出假说”柔肝方降低肝内Th17的IL-17A和FBRS表达,下调HSC的TGFβ受体和TGFβ1表达,抑制HSC活化”。拟开展:柔肝方对ConA诱导HF小鼠肝内Th17的IL-17A、FBRS表达和HSC的MAPK活化、TGFβ1与TGFβ受体表达的影响;分别构建IL-17A、FBRS沉默小鼠,观察ConA体内干预对HSC的MAPK、TGFβ1、TGFβ受体表达和柔肝方作用;体外沉默小鼠HSC的TGFβ1、TGFβ受体,观察IL-17A、FBRS刺激后MAPK活化、HSC活化和柔肝方作用,明确柔肝方多靶点抗HF免疫机制。
英文摘要
Hepatic fibrosis (HF) in chronic hepatitis B is positively related to the expression of FBRS and Th17. IL-17A and FBRS secreted by Th17 up-regulate the levels of TGFβ receptor and TGF β1 in HSC by activating the MAPK signal and then result in HSC activation. The Rougan Recipe composed of Traditional Chinese Medicine of nourishing yin and promoting blood circulation is efficient in the treatment of Hepatic fibrosis (HF) in chronic hepatitis B, which may inhibit the activation of HSC and decrease Th17 and FBRS expression. The hypothesis is proposed that" Rougan Recipe reduces the level of IL-17A and FBRS expressed by Th17 in the liver and down-regulates the expression of TGFβ receptor and TGF β1 in HSC, and then inhibit the activation of HSC. . The following studies will be carried out: the effects of Rougan Recipe on levels of IL-17A and FBRS expressed by Th17 in the liver, MAPK activation and levels of TGFβ receptor and TGF β1 in HSC in HF model mice induced by ConA will be examined; IL-17A silenced mice FBRS silenced mice will be constructed and then MAPK activation and levels of TGFβ receptor and TGF β1 in HSC were observed interrupting by ConA in vivo and Rougan Recipe's effects ; TGF beta 1, TGF beta receptor expressed by HSC are respectively silenced in vitro, and then MAPK activation and the activation of HSC and Rougan Recipe's effects will be studied. The mechanism of anti-hepatic hepatitis by multi targets will be clarified.
