网络出版日期: 2014-10-28
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
Online published: 2014-10-28
Supported by
sTNFr-13 Horizontal Subject,101005.335
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
戴绘娟 , 翟秀宇 , 李大伟 , 等 . 腺苷A2A受体激动剂CGS21680对ConA诱导的小鼠急性肝损伤的影响[J]. 上海交通大学学报(医学版), 2014 , 34(10) : 1459 . DOI: 10.3969/j.issn.1674-8115.2014.10.008
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
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