miR-126 通过 VEGF-Notch 信号通路促进青光眼大鼠视网膜神经节细胞凋亡。
MiR-126 facilitates apoptosis of retinal ganglion cells in glaucoma rats via VEGF-Notch signaling pathway.
机构信息
Department of Ophthalmology, Yantaishan Hospital, Yantai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Sep;24(17):8635-8641. doi: 10.26355/eurrev_202009_22800.
OBJECTIVE
The aim of this study was to explore the effect of micro ribonucleic acid (miR)-126 on the apoptosis of retinal ganglion cells in glaucoma rats via the vascular endothelial growth factor (VEGF)-Notch signaling pathway.
MATERIALS AND METHODS
A total of 36 Sprague-Dawley (SD) rats were randomly divided into three groups, including normal group (n=12), model group (n=12) and miR-126 antagomir group (n=12). Rats in normal group did not receive any treatment. In model group and miR-126 antagomir group, the rats were used to establish glaucoma models and intervened with normal saline and miR-126 antagomir, respectively. Intraocular pressure was detected at the completion of modeling and the last intervention, at 7 days after which samples were taken. Western blotting was adopted to detect the relative protein expressions of Notch1 and Notch2. The content of VEGF was examined via enzyme-linked immunosorbent assay (ELISA). Quantitative polymerase chain reaction (qPCR) was carried out to detect the messenger RNA (mRNA) expressions of VEGF, Notch1 and Notch2. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to detect cell apoptosis.
RESULTS
After modeling, intraocular pressure in model group and miR-126 antagomir group was significantly higher than that in normal group (p<0.05). At the end of the intervention, intraocular pressure in miR-126 antagomir group was notably lower than that in model group (p<0.05). VEGF content in model group and miR-126 antagomir group was notably higher than that in normal group (p<0.05). However, it was markedly lower in miR-126 antagomir group than model group (p<0.05). Model group exhibited remarkably higher protein expressions of Notch1 and Notch2 than normal group (p<0.05). However, the protein expressions of Notch1 and Notch2 in miR-126 antagomir group were evidently reduced (p<0.05). Besides, the mRNA expressions of VEGF, Notch1 and Notch2 in model group were significantly higher than those in normal group (p<0.05). However, they were significantly lower in miR-126 antagomir group than those in model group (p<0.05). Furthermore, the apoptosis rate in model group was distinctly higher than that in normal group (p<0.05). However, it was notably lower in miR-126 antagomir group than model group (p<0.05).
CONCLUSIONS
MiR-126 facilitates the apoptosis of retinal ganglion cells in glaucoma rats by promoting the VEGF-Notch signaling pathway.
目的
本研究旨在探讨微小 RNA-126（miR-126）通过血管内皮生长因子（VEGF）-Notch 信号通路对青光眼大鼠视网膜神经节细胞凋亡的影响。
材料与方法
将 36 只 Sprague-Dawley（SD）大鼠随机分为三组，包括正常组（n=12）、模型组（n=12）和 miR-126 反义寡核苷酸组（n=12）。正常组大鼠不接受任何治疗。在模型组和 miR-126 反义寡核苷酸组中，分别采用生理盐水和 miR-126 反义寡核苷酸进行干预，建立青光眼模型。在建模完成和最后一次干预后检测眼内压，干预后 7 天取样本。采用 Western blot 检测 Notch1 和 Notch2 的相对蛋白表达。酶联免疫吸附试验（ELISA）检测 VEGF 含量。采用实时定量聚合酶链反应（qPCR）检测 VEGF、Notch1 和 Notch2 的信使 RNA（mRNA）表达。采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）法检测细胞凋亡。
结果
建模后，模型组和 miR-126 反义寡核苷酸组的眼内压明显高于正常组（p<0.05）。干预结束时，miR-126 反义寡核苷酸组的眼内压明显低于模型组（p<0.05）。模型组和 miR-126 反义寡核苷酸组的 VEGF 含量明显高于正常组（p<0.05），但 miR-126 反义寡核苷酸组明显低于模型组（p<0.05）。模型组 Notch1 和 Notch2 的蛋白表达明显高于正常组（p<0.05），而 miR-126 反义寡核苷酸组的 Notch1 和 Notch2 蛋白表达明显降低（p<0.05）。此外，模型组 VEGF、Notch1 和 Notch2 的 mRNA 表达明显高于正常组（p<0.05），但 miR-126 反义寡核苷酸组明显低于模型组（p<0.05）。此外，模型组的细胞凋亡率明显高于正常组（p<0.05），但 miR-126 反义寡核苷酸组明显低于模型组（p<0.05）。
结论
miR-126 通过促进 VEGF-Notch 信号通路促进青光眼大鼠视网膜神经节细胞凋亡。
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