【摘要】 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。更多还原

【Abstract】 Chloroquine can suppress immune response,and is used for the treatment of some autoimmune disease,such as rheurmatoid arthritis and system lupus erythematosus.The purpose of this project is to investigate the effect of chloroquine on autoimmune hepatitis in mice and the potential mechanism.Mouse liver injury model was induced by intravenous injection of Con A followed by intraperitoneal injection of chloroquine or PBS 1hour later.Liver injury was assessed by hematoxylin and eosin(H&E)staining of liver sections and the level of serum glutamic pyruvic transaminase(GPT)activities.IFN-γand TNF-αlevels were measured by ELISA;The expression of LC3-Ⅱ and P62 in mice liver were detected by Western blot analysis.Compared with the Con A injection group,serum levels of IFN-γ,TNF-αand GPT were increased in the mice treated with Con A plus chloroquine.In addition,the liver injury was more serious in Con A plus chloroquine group;Autophagy was activated in Con A induced hepatitis indicated with increased LC3-Ⅱand decreased P62,while chloroquine could inhibit the autophagy during the process.We conclude that chloroquine can aggravate Con A-induced autoimmune liver injury through inhibiting autophagy in the liver.更多还原