[1]高莎,沈玺.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[J].眼科新进展,2022,42(7):510-513.[doi:10.13389/j.cnki.rao.2022.0104]
　GAO Sha,SHEN Xi.Protective effect of adenosine A2A receptor antagonist ZM241385 on retinal photoreceptor cells in mice with retinal detachment[J].Recent Advances in Ophthalmology,2022,42(7):510-513.[doi:10.13389/j.cnki.rao.2022.0104]
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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/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
42卷
期数:
2022年7期
页码:
510-513
栏目:
实验研究
出版日期:
2022-07-05

文章信息/Info

Title:
Protective effect of adenosine A2A receptor antagonist ZM241385 on retinal photoreceptor cells in mice with retinal detachment
作者:
高莎; 沈玺
200025　上海市，上海交通大学医学院附属瑞金医院眼科
Author(s):
GAO Sha; SHEN Xi
Department of Ophthalmology,Ruijin Hospital,Affiliated to Medical School of Shanghai Jiaotong University,Shanghai 200025,China
关键词:
视网膜脱离; 腺苷A2A受体; 谷氨酰胺合成酶; 单核细胞趋化蛋白-1; 肿瘤坏死因子-α; 光感受器细胞
Keywords:
retinal detachment;  adenosine A2A receptor;  glutamine synthase;  monocyte chemoattractant protein-1;  tumor necrosis factor-α;  photoreceptor cells
分类号:
R774
DOI:
10.13389/j.cnki.rao.2022.0104
文献标志码:
A
摘要:
目的　探讨腺苷A2A受体（A2AR）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　A2AR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。
Abstract:
Objective　To explore the protective effect of adenosine A2A receptor (A2AR) 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 A2AR 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　A2AR 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.

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备注/Memo

备注/Memo:
国家自然科学基金项目（编号：81970805）
更新日期/Last Update: 2022-07-05