小剂量顺铂通过下调Th17细胞频率缓解小鼠自身免疫性肝炎  

Low-dose cisplatin alleviates autoimmune hepatitis by downregulating Th17 cells frequency in mice

作　　者：刘青青[1] 田海霞 康行 田艳 杨昊 罗旭光[1] 樊卫平[1] LIU Qingqing;TIAN Haixia;KANG Xing;TIAN Yan;YANG Hao;LUO Xuguang;FAN Weiping(Department of Microbiology and Immunology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学微生物与免疫教研室,太原030001

出　　处：《免疫学杂志》2021年第1期46-50,共5页Immunological Journal

基　　金：山西省应用基础研究(自然科学基金)面上项目(201901D111194)。

摘　　要：目的探索小剂量顺铂对小鼠自身免疫性肝炎(AIH)Th17细胞的影响及相关机制。方法将24只小鼠随机分为正常组(normal group)、AIH+顺铂组(AIH+Cisplatin group)和AIH+生理盐水组(AIH+NS group)。后2组利用S100/FCA建立小鼠AIH模型后,分别腹腔注射0.2 ml含1 mg/kg的顺铂和生理盐水,每周1次连续3周。检测小鼠血清转氨酶ALT、AST水平;HE染色观察小鼠肝组织病理改变;流式细胞术检测脾细胞中Th17细胞频率;免疫组化检测肝组织IL^(-1)7A的表达;Western blot检测肝组织中STAT3和磷酸化STAT3的表达。结果与AIH+NS组相比,AIH+Cisplatin组转氨酶明显下降、肝组织病理好转、IL^(-1)7A表达及Th17细胞比例下调、磷酸化STAT3的表达下降。结论小剂量顺铂可能通过抑制STAT3信号下调Th17细胞频率并减少IL^(-1)7A的分泌,缓解小鼠AIH。To explore the effects of low dose cisplatin on autoimmune hepatitis(AIH)in mice and its mechanism,24 mice were recruited and randomly divided into normal group,AIH+cisplatin group and AIH+saline group.For the latter two groups,S100/FCA was used to establish a mouse AIH model,and 0.2 ml cisplatin and saline were injected intraperitoneally,once a week for 3 weeks.Serum ALT and AST levels of mice were applied as readout of liver damage;pathological changes of liver tissues were observed through HE staining;the percentage of Th17 cells in splenocyes was detected by intracellular staining;the expression of IL^(-1)7A in liver tissue was explored by immunohistochemistry;the STAT3 and phosphorylated STAT3 protein in liver tissue were quantitated by Western blotting.Data showed that cisplatin could decrease transaminase level,improve liver pathology,downregulate the expression of IL^(-1)7A and Th17 cells,and decrease the level of phosphorylated STAT3 in AIH mice,as compared with AIH+NS group.Therefore,low-dose cisplatin may alleviate AIH in mice by inhibiting STAT3 signal,down-regulating Th17 cells frequency and reducing IL^(-1)7A secretion.

关 键 词：顺铂 自身免疫性肝炎 TH17细胞 IL-17A STAT3 

分 类 号：R392.9[医药卫生—免疫学]