Toll样受体3介导的信号通路在原发性胆汁性肝硬化模型中的作用

目的 初步探索Toll样受体3(TLR3)介导的信号通路在原发性胆汁性肝硬化(PBC)发病中的作用以及趋化因子受体3(CXCR3)对其影响.方法 6～8周雌性C57BL/6野生鼠和CXCR3基因敲除(CXCR3-/-)鼠,腹腔注射5 mg/kg的聚肌胞(poly I:C),每周2次,第8、16、24周收集小鼠肝脏标本,...

Role of Toll-Like Receptor 3 Signaling Pathways in the Induction of Primary Biliary Cirrhosis

Objective To investigate whether TLR3 signaling pathway were involved in the pathogenesis of PBC.Methods Female C57BL/6 wide-type and CXCR3-/- mice were injected with 5 mg/kg of poly I：C intra-peritoneally twice a week for 24 consecutive weeks.Liver specimens were collected to evaluate the degree of cell infiltration.Autoantibodies,including AMA,were assayed by ELISA.The liver expressions of TLR3,TRIF and p-NFκB p65 in mice model and control mice were evaluated by immunoblotting.Results The liver protein level of TLR3 was elevated in PBC mice.There was no significant difference in TLR3 level among different periods or between wide-type（WT） mice and CXCR3-/- mice.The level of TLR3 was decreased in PBC CXCR3-/- mice of 16 weeks and 24 weeks period.There was no significant difference in TRIF level between PBC mice and control mice or between WT mice and CXCR3-/- mice.There was no significant difference of p-NFκB p65 level between PBC mice and control mice.The level of p-NFκB p65 in CXCR3-/- PBC mice was higher than control,which was increased evidently over 16 weeks period.Conclusions TLR3 signaling pathway might be involved in the pathogenesis of PBC mice.NF-κB might not be the key transcription factor in the development of PBC.CXCR3 have no great effect on TLR3 signaling pathways in the induction of PBC.