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氯喹(chloroquine,CQ)可抑制免疫反应,偶用于类风湿性关节炎、系统性红斑狼疮等自身免疫性疾病的治疗,但氯喹对自身免疫性肝炎的影响目前尚不明确。本研究拟探讨CQ对小鼠自身免疫性肝损伤的影响及可能机制。小鼠尾静脉注射Con A建立小鼠肝损伤模型,1h后,腹腔注射CQ或等体积PBS。观察小鼠生存状况,在不同时间点收集血清和肝组织,采用赖氏法检测血清谷丙转氨酶(GPT)水平;ELISA方法检测血清细胞因子IFN-γ及TNF-α含量;HE染色观察肝脏病理损伤情况;免疫印迹检测小鼠肝脏自噬水平指标LC3-Ⅱ和P62。结果显示,Con A+CQ组小鼠血清中GPT水平显著高于Con A组,且病理切片染色显示Con A+CQ组肝脏损伤较Con A组更严重;Con A+CQ注射组小鼠的存活率明显低于仅注射Con A组(P<0.0001);Con A+CQ组小鼠血清中炎性细胞因子IFN-γ和TNF-α的分泌高于Con A组;CQ可抑制Con A刺激诱导的小鼠肝脏自噬水平升高。氯喹可加重Con A诱导的自身免疫性肝损伤,其机制可能是通过抑制肝脏自噬水平从而加剧小鼠肝脏损伤。
Chloroquine (CQ) can inhibit the immune response, even for rheumatoid arthritis, systemic lupus erythematosus and other autoimmune diseases, but the impact of chloroquine on autoimmune hepatitis is not yet clear. This study was to investigate the effect of CQ on autoimmune liver injury in mice and its possible mechanism. Mice were injected with Con A through the tail vein to establish a mouse model of liver injury. One hour later, CQ or equal volume of PBS was injected intraperitoneally. Serum alanine aminotransferase (GPT) levels were measured by Lai’s method. Serum levels of IFN-γ and TNF-α were detected by ELISA. Liver pathology was observed by HE staining Injury. Western blotting was used to detect the levels of liver autophagy LC3-Ⅱ and P62 in mice. The results showed that the level of GPT in Con A + CQ group was significantly higher than that in Con A group, and the histological staining showed that the liver injury in Con A + CQ group was more serious than that in Con A group. The survival of Con A + CQ group (P <0.0001). The secretion of inflammatory cytokines IFN-γ and TNF-α in Con A + CQ group was higher than that in Con A group. CQ inhibited Con A-induced induction Mouse liver autophagy levels increased. Chloroquine can aggravate Con A-induced autoimmune liver injury, and its mechanism may be to exacerbate liver damage in mice by inhibiting liver autophagy.