王彦彦,张艳艳,易全勇

目的：探讨腺苷A2A受体拮抗剂KW-6002对链脲佐菌素（STZ）诱导的糖尿病视网膜病变（DR）的作用及可能机制。方法：采用55mg/kg STZ连续5天腹腔注射建立C57BL/6小鼠糖尿病模型。小鼠随机分为对照组、糖尿病模型组(STZ组)和KW-6002治疗组（DB+KW-6002组）。KW-6002组自确诊糖尿病开始以10μg/g腹腔注射，每周1次,连续4周。采用HE染色观察视网膜病理学改变，免疫荧光染色检测胶质纤维酸性蛋白（GFAP）、小胶质细胞标志物（IBA-1）、细胞间粘附分子-1(ICAM-1)的表达。结果：HE染色显示STZ组视网膜结构出现不同程度异常，神经节细胞层和内外核层细胞排列紊乱、数量减少、变性坏死，KW-6002治疗组病变程度较STZ组减轻。免疫荧光分析显示:STZ组GFAP阳性细胞密度显著升高,提示Müller细胞活化；IBA-1阳性细胞密度增加,小胶质细胞活化明显增多；ICAM-1阳性细胞密度上调，提示血管炎症反应增强。KW-6002治疗显著抑制GFAP(P<0.01)/IBA- 1(P<0.01)、ICAM-1(P<0.01)的过度表达。结论：腺苷A2A受体拮抗剂KW-6002能够通过抑制小胶质细胞活化、减轻视网膜炎症反应,对STZ诱导的早期糖尿病视网膜病变发挥一定的保护作用。

DR；腺苷A2A受体；小胶质细胞

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