TLR2/4配体增强的非特异性肝脏炎症对BALB/c小鼠自身免疫性肝炎的影响

目的:探索非特异性肝脏炎症诱导BALB/c小鼠产生自身免疫性肝炎(AIH)的原因。方法:尾静脉注射质粒pCYP2D6、pcDNA3.1和psTLR2/4,腹腔重复注射四氯化碳(CCl_4)。ELISA检测抗CYP2D6抗体和自身抗体水平;HE染色检测肝脏炎症情况;天狼星红染色检测肝脏纤维化情况。结果:CCl_4引发BALB/c小鼠产生非特异性肝脏炎症,TLR2/4配体增强了这种炎症。停止注射CCl_4后,非特异性肝脏炎症消失,但是却促进模拟抗原人CYP2D6诱导产生自身免疫应答、自身免疫性肝炎和肝纤维化,且TLR2/4配体增强了这些变化。结论:TLR2/4增强的肝脏非特异性炎症在BALB/c小鼠自身免疫性肝炎的启动和发展中可能发挥了重要作用。

Effect of TLR2/4 ligand-enhanced non-specific liver inflammation on autoimmune hepatitis in BALB/c mice

AIM:To explore the role of non-specific liver inflammation in inducing autoimmune hepatitis(AIH)in BALB/c mice.METHODS:The plasmids pCYP2D6,pcDNA3.1 and psTLR2/4 were administered by tail vein injection.The carbon tetrachloride(CCl4)was injected in the abdominal cavity.The autoimmune response was measured by ELISA.The liver inflammation was observed by HE staining.The liver fibrosis was evaluated by Sirius red staining.RESULTS:CCl4 induced non-specific liver inflammation in the BALB/c mice,and TLR2/4 ligand enhanced the inflammatory responses.After the repeated injection of CCl4 stopped,the non-specific liver inflammation disappeared,but CCl4 promoted autoimmune response,autoimmune hepatitis and liver fibrosis induced by mimetic antigen human CYP2D6,and TLR2/4 ligand enhanced these changes.CONCLUSION:TLR2/4-amplified liver non-specific inflammation may play an important role in the initiation and progression of autoimmune hepatitis in BALB/c mice.