腺苷A2A受体激动剂CGS21680对ConA诱导的小鼠急性肝损伤的影响

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

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。

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 C57 BL /6 male mice were randomly divided into the ConA group andCGS21680 ＋ConA group. Mice of the ConA group were given ConA of 20 mg /kg by caudal vein injection. M ice of the CGS21680 ＋Con A group were given adenosine A2 A receptor agonist CGS21680 of 2. 1 mg /kg by intraperitoneal injection and then were given ConA of20 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 ofCD4^＋Tcells in liver tissues decreased. Conclusion Pretreatment by the adenosine A2 A receptor agonistCGS21680 can significantly relieve the ConA-induced acute hepatic injury of mice. T his may be relevant to activating A2 A receptor on the surface ofCD4^＋Tcells by the CGS21680 and inhibiting the release of proinflammatory factors.