上海交通大学学报(医学版)

• 论著(基础研究) • 上一篇    下一篇

腺苷A2A受体激动剂CGS21680对ConA诱导的小鼠急性肝损伤的影响

戴绘娟1,翟秀宇2,李大伟1,张 江1,张健健1,张建军1   

  1. 1.上海交通大学 医学院附属仁济医院肝脏外科, 上海 200127; 2.吉林大学第一医院泌尿外科, 吉林 130021
  • 出版日期:2014-10-28 发布日期:2014-10-28
  • 通讯作者: 张建军, 电子信箱: zhangjianjun@medmail.com.cn。
  • 作者简介:戴绘娟(1988—), 女, 硕士; 电子信箱: daihuijuan1988@163.com。
  • 基金资助:

    sTNFr-13横向课题(101005.335)

Effects of adenosine A2A receptor agonist CGS21680 on concanavalin-induced acute hepatic injury of mice

DAI Hui-juan1, ZHAI Xiu-yu2, LI Da-wei1, ZHANG Jiang1, ZHANG Jian-jian1, ZHANG Jian-jun1   

  1. 1.Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2.Department of Urology, the First Hospital of Jilin University, Jilin 130021, China
  • Online:2014-10-28 Published:2014-10-28
  • Supported by:

    sTNFr-13 Horizontal Subject,101005.335

摘要:

目的 探讨腺苷A2A受体激动剂CGS21680对伴刀豆球蛋白(ConA)引起的小鼠急性肝损伤的影响及其可能机制。方法 雄性C57BL/6小鼠随机分为ConA组和CGS21680+ConA组。ConA组小鼠经尾静经脉注射ConA (20 mg/kg),CGS21680+ConA组小鼠经腹腔注射腺苷A2A受体激动剂CGS21680 (2.1 mg/kg)10 min后再经尾静经脉注射ConA (20 mg/kg)。检测小鼠血清谷丙转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ干扰素(IFN-γ)、白介素-4 (IL-4)和肿瘤坏死因子-α (TNF-α)水平;光学显微镜下观察肝组织病理改变,评估肝损伤程度;采用流式细胞仪检测肝组织单个核细胞(MNCs)中CD4+T细胞IFN-γ和IL-4的表达。结果 与ConA组比较,CGS21680+ConA组小鼠血清ALT、AST、IFN-γ、IL-4和TNF-α水平显著降低;肝脏组织中炎症细胞浸润明显减少,肝脏损伤程度较轻;肝组织CD4+T细胞IFN-γ和IL-4的表达减少。结论 腺苷A2A受体激动剂CGS21680预处理能够显著减轻ConA引起的小鼠急性肝损伤,这可能与CGS21680激活CD4+ T细胞表面的A2A受体进而抑制促炎因子的释放有关。

关键词: 刀豆蛋白, 腺苷A2A受体激动剂, 急性肝损伤, 小鼠

Abstract:

Objective To investigate the effects of adenosine A2A receptor agonist CGS21680 on the concanavalin (ConA)-induced acute liver injury of mice and possible mechanisms. Methods C57BL/6 male mice were randomly divided into the ConA group and CGS21680+ConA group. Mice of the ConA group were given ConA of 20 mg/kg by caudal vein injection. Mice of the CGS21680+ConA group were given adenosine A2A receptor agonist CGS21680 of 2.1 mg/kg by intraperitoneal injection and then were given ConA of 20 mg/kg by caudal vein injection after 10 min. Levels of serum ALT, AST, IFN-γ, IL-4, and TNF-α were detected. Pathologic changes of liver tissue were measured under the optical microscope and the level of hepatic injury was evaluated. Expressions of IFN-γ and IL-4 of CD4+T cells in mononuclear cells (MNCs) were detected by the flow cytometry. Results Compared to the ConA group, levels of serum ALT, AST, IFN-γ, IL-4, and TNF-α of the CGS21680+ConA group significantly decreased; inflammatory cell infiltration of liver tissues significantly decreased; hepatic injuries were mild; and expressions of IFN-γ and IL-4 of CD4+T cells in liver tissues decreased. Conclusion Pretreatment by the adenosine A2A receptor agonist CGS21680 can significantly relieve the ConA-induced acute hepatic injury of mice. This may be relevant to activating A2A receptor on the surface of CD4+ T cells by the CGS21680 and inhibiting the release of proinflammatory factors.

Key words: concanavalin, acute liver injury, adenosine A2A receptor agonist, mice