腺苷A2A受体（A2AR）拮抗剂ZM241385对视网膜脱离动物模型视网膜光感受器细胞的保护作用

目的　探讨腺苷A_2A受体（A_2AR）拮抗剂ZM241385对视网膜脱离（RD）动物模型视网膜光感受器细胞的保护作用。方法　选取健康雄性SPF级C57BL/6J小鼠48只作为研究对象。将实验小鼠随机分为对照+二甲基亚砜（DMSO）组、对照+ZM241385组、RD+DMSO组、RD+ZM241385组，每组12只。RD模型建立后，实验小鼠立即腹腔注射ZM241385（3 mg·kg^-1，剂量不超过0.2 mL）或同体积DMSO，连续给药3 d。采用免疫荧光染色检测视网膜中Müller细胞谷氨酰胺合成酶(GS)的表达，Western blot检测单核细胞趋化蛋白（MCP）-1、肿瘤坏死因子（TNF）-α、Cleaved caspase 3和B细胞淋巴瘤抗体（Bcl）-2的表达。结果　免疫荧光染色结果显示:RD+DMSO组小鼠视网膜Müller细胞GS荧光强度较对照+DMSO组显著降低，而RD+ZM241385组小鼠视网膜Müller细胞GS荧光强度较RD+DMSO组显著升高。RD+DMSO组小鼠视网膜MCP-1、TNF-α蛋白表达水平较对照+DMSO组均显著升高，差异均有统计学意义（均为P<0.001），而RD+ZM241385组小鼠视网膜MCP-1、TNF-α蛋白表达水平较RD+DMSO组均显著降低，差异均有统计学意义（均为P<0.001）。与对照+DMSO组相比，RD+DMSO组小鼠视网膜Cleaved caspase 3蛋白表达水平显著升高，Bcl-2蛋白表达水平显著下降，差异均有统计学意义（均为P<0.001）。而与RD+DMSO组相比，RD+ZM241385组小鼠视网膜Cleaved caspase 3蛋白表达水平显著下降，Bcl-2蛋白表达水平显著升高，差异均有统计学意义（均为P<0.001）。结论　A_2AR拮抗剂ZM241385通过促进RD小鼠视网膜Müller细胞GS表达，抑制炎症细胞因子MCP-1、TNF-α的表达，缓解光感受器细胞凋亡。

Protective effect of adenosine A2A receptor antagonist ZM241385 on retinal photoreceptor cells in mice with retinal detachment

Objective　To explore the protective effect of adenosine A_2A receptor (A_2AR) antagonist ZM241385 on retinal photoreceptor cells in mice with retinal detachment (RD). Methods　Forty-eight healthy SPF-grade C57BL/6J male mice were selected and randomly divided into the control + dimethyl sulfoxide (DMSO) group, control + ZM241385 group, RD + DMSO group, and RD + ZM241385 group, with 12 mice in each group. After RD modeling, mice were intraperitoneally injected with the A_2AR antagonist ZM241385 (3 mg·kg^-1) at a dose of not more than 0.2 mL or an equivalent volume of DMSO continuously for 3 days. Glutamine synthase (GS) expression in retinal Müller cells of mice in each group was evaluated with immunofluorescence. The expression levels of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, Cleaved caspase 3, and B-cell lymphoma (Bcl)-2 were detected with Western blot. Results　Immunofluorescence results showed that the GS fluorescence intensity of retinal Müller cells in the RD + DMSO group was significantly lower than that in the control + DMSO group and that the GS fluorescence intensity of retinal Müller cells in the RD + ZM241385 group was significantly higher than that in the RD + DMSO group. The expression levels of MCP-1 and TNF-α proteins in the RD + DMSO group were significantly higher than those in the control + DMSO group (both P<0.001), while the expression levels of MCP-1 and TNF-α proteins in the RD + ZM241385 group were significantly lower than those in the RD + DMSO group (both P<0.001). Compared with the control + DMSO group, the expression level of Cleaved caspase 3 protein in the RD + DMSO group was significantly increased, and the expression level of Bcl-2 protein was significantly decreased (both P<0.001). Compared with the RD + DMSO group, the expression level of Cleaved caspase 3 protein in the RD + ZM241385 group was significantly decreased, and the expression level of Bcl-2 protein was significantly increased (both P<0.001). Conclusion　A_2AR antagonist ZM241385 alleviates the apoptosis of photoreceptor cells in RD mice by promoting the expression of GS in retinal Müller cells and inhibiting the expression of inflammatory cytokines MCP-1 and TNF-α.