雷帕霉素通过下调氧诱导性视网膜病变小鼠模型中环细胞蛋白 D1 预防视网膜新生血管形成。
Rapamycin prevents retinal neovascularization by downregulation of cyclin D1 in a mouse model of oxygen-induced retinopathy.
机构信息
Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Ophthalmology, Shenyang Aier Eye Hospital, Shenyang City, China.
出版信息
BMC Ophthalmol. 2020 Feb 3;20(1):44. doi: 10.1186/s12886-020-1325-5.
BACKGROUND
Rapamycin (RAPA) is a potent angiogenic inhibitor and the aim of this study is to identify the inhibitory effect of RAPA on retinal neovascularization (RNV) in experimental oxygen-induced retinopathy (OIR).
METHODS
Forty-two 7-day-old C57BL/6 J mice were randomly divided into normoxia control group (14 mice), OIR group (14 mice), and rapamycin (RAPA) group. OIR model was induced in OIR and RAPA group. Vehicle and RAPA (2 mg/kg/d) was injected intraperitoneally daily from postnatal day 12 (P12) in OIR and RAPA groups, respectively. RNV was evaluated using fluorescence angiography and histopathology on P17. Non-perfused areas of retina were analyzed by Image-Pro plus 6.0 software. Retinal expression of cyclin D1 was detected both at mRNA and protein levels.
RESULTS
RAPA treatment significantly decreased RNV, non-perfused areas and number of endothelial cell nuclei breaking through the internal limiting membrane (ILM) in OIR mice. Moreover, RAPA decreased activation of cyclin D1 in retina caused by OIR.
CONCLUSION
RAPA can inhibit RNV by downregulating the expression of cyclin D1, which indicates its therapeutic potential in treating RNV-related diseases.
背景
雷帕霉素（RAPA）是一种有效的血管生成抑制剂，本研究旨在确定 RAPA 对实验性氧诱导视网膜病变（OIR）中视网膜新生血管（RNV）的抑制作用。
方法
42 只 7 日龄 C57BL/6J 小鼠随机分为常氧对照组（14 只）、OIR 组（14 只）和雷帕霉素（RAPA）组。OIR 组和 RAPA 组诱导 OIR 模型。OIR 组和 RAPA 组分别于 P12 开始每日腹腔内注射载体和 RAPA（2mg/kg/d）。P17 时采用荧光血管造影和组织病理学评估 RNV。用 Image-Pro plus 6.0 软件分析视网膜无灌注区。检测视网膜中环细胞 D1 的 mRNA 和蛋白水平。
结果
RAPA 治疗可显著减少 OIR 小鼠的 RNV、无灌注区和穿过内界膜（ILM）的内皮细胞核数目。此外，RAPA 可降低 OIR 引起的视网膜中环细胞 D1 的激活。
结论
RAPA 可通过下调 cyclin D1 的表达抑制 RNV，表明其在治疗与 RNV 相关疾病方面具有治疗潜力。
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