腺苷A2A受体在小鼠视网膜病理性血管形成中的作用被引量：2

Adenosine A2A receptor and retinal pathological neovascularization in mice

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摘要目的观察腺苷A2A受体在小鼠视网膜病理性血管形成中的作用。方法将202只新生小鼠分为空气组和氧诱导视网膜病变（OIR）组，分别为66、136只。空气组再分为A2A基因敲除空气组、野生型空气组、咖啡因饮水空气组，分别为18、24、24只，均置于正常空气浓度中饲养。OIR组再分为野生型氧诱导组、A2A基因敲除氧诱导组及咖啡因饮水氧诱导组，分别为48、24、64只，建立小鼠OIR模型。行视网膜石蜡切片，观察病理性新生血管反应；荧光定量聚合酶链反应（PCR）检测小鼠视网膜组织中A2A和血管内皮生长因子（VEGF）的mRNA表达。将0．1、0．3、1．0g／L剂量的腺苷受体抑制剂咖啡因溶于咖啡因饮水氧诱导组哺乳母鼠饮用水中，定量分析不同剂量及当剂量为1．0g／L时，出生后0～17、0～7、7～17、7～12、12～17d等不同饮水时间窗的小鼠视网膜无血管区面积比。结果与野生型氧诱导组相比，A2A基因敲除氧诱导组视网膜中周部无血管区面积明显减少，差异有统计学意义（t=7．694，P〈0．001）；突破内界膜的细胞数也明显减少，差异有统计学意义（t=7．747，P〈0．001）。荧光定量PCR检测结果显示，与野生型空气组比较，野生型氧诱导组小鼠视网膜中A2A、VEGFmRNA表达量均增高，差异有统计学意义（t=4．036、2．230，P〈0．05）。与野生型氧诱导组比较，A2A基因敲除氧诱导组小鼠视网膜中VEGFmRNA表达明显下降，差异有统计学意义（t=3．122，P〈0．01）。与野生型氧诱导组比较，0．1、1．0g／L剂量组小鼠视网膜无血管区面积明显减少，差异有统计学意义（t=2．397、4．533，P〈0．05）；出生后0～17、0～7d饮水时间窗的小鼠视网膜无血管区面积明显减少，差异有统计学意义（t=4．070、2．399，P〈0．05）。结论腺苷A2A受体在诱导小鼠视网膜病理性血管形成时表达升高。腺苷A2A受体可调节VEGF的表达。A2A受体失活特异性抑制病理性视网膜新生血管。 Objective To investigate the role of adenosine A2A receptor plays in retinal pathological neovascularization in mice. Methods A total of 202 mice were divided into room air group （n = 66） and oxygen induced retinopathy （OIR） group （n--136）. Among room-air group, there were 18 A2A knock out （KO） mice （KO subgroup） and 24 C57B1./6 mice as wide type （wide type subgroup）. OIR group were divided into OIR control subgroup （n=48）, A2A- OIR subgroup （n=24） and Caffeine-OIR subgroup （n~ 64）. The retinal neovascularization of OIR group was induced by oxygen. The pathological neovascularization was determined by retinal sections. Fluorescent quantitative polymerase chain reaction （PCR） was used to measure the mRNA expression of A2A and vascular endothelial growth factor （VEGF）. 0. 1, 0.3, 1.0 g/L Caffeine was dissolve in drinking water of lactating females in Caffeine-OIR subgroup, non perfusion areas of retina in mice at the age of 0 - 17, 0 7, 7 - 17, 7 - 12, and 12 - 17 days were analyzed in different dosage and when the dosage as 1.0 g/L. Results Compared with OIR control subgroup, the retinal non-perfusion areas and the numbers of endothelial cell nuclei breaking through the internal limiting membrane in A2A- OIR subgroup were reduced significantly （t= 7.694, 7. 747; P〈 0. 001）. Compared with wide type subgroup, the level of A2A and VEGF mRNA in OIR control subgroup increased significantly （t=4. 036, 2. 230; P〈0. 05）. Compared with OIR control subgroup, the level of VEGF mRNA in A2A OIR subgroup decreased significantly （t=3. 122, P〈0.01）. Compared with OIRcontrol subgroup, the retinal non-perfusion areas in mice at the dosage of 0. 1 and 1.0 g/L （t= 2. 397, 4. 533） and at the age of 0 17, 0 - 7 days when the dosage as 1.0 g/L （t=4.070, 2. 399） were reduced significantly （P〈 0.05）. Conclusions The expression of adenosine A2A receptor increases in oxygen induced retinal pathological neovascularization.. Adenosine A2A receptor may regulate the expression of VEGF. A2A receptor inactivation can inhibit oxygen induced retinal pathological neovascularization.

作者周容汪村王萌林冰李英姿孙祖华冯浩刘晓玲

机构地区温州医科大学附属眼视光医院

出处《中华眼底病杂志》 CAS CSCD 北大核心 2013年第6期580-584,共5页 Chinese Journal of Ocular Fundus Diseases

基金基金项目：国家自然科学基金青年科学基金（81100672）浙江省自然科学基金（LY12H12007）

关键词视网膜新生血管化病理生理学受体腺苷A2A 咖啡因 Retinal neovascularization/physiopathology Receptor, adenosine A2A Caffeine

分类号 R774.12 [医药卫生—眼科]

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