去铁胺通过激活 HIF-1α/VEGF-A 通路减轻大鼠蛛网膜下腔出血后视网膜缺氧。
Activation of HIF-1α/VEGF-A pathway by deferoxamine ameliorates retinal hypoxia in a rat subarachnoid hemorrhage model.
机构信息
Tibet Autonomous Region Eye Center, Tibetan Medicine Hospital of Tibet Autonomous Region, Tibet.
Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing.
出版信息
Neuroreport. 2022 Nov 2;33(16):690-696. doi: 10.1097/WNR.0000000000001835. Epub 2022 Sep 19.
BACKGROUND AND PURPOSE
Subarachnoid hemorrhage (SAH) is associated with sustained vasoconstriction in retinal vessels and vasoconstriction leads to retinal ischemia and hypoxia. Our previous finding also revealed the changes in hypoxia-related elements in the retina after SAH, further lending weight to the hypothesis that retinal vasospasm and hypoxia after SAH. Deferoxamine is a high-affinity iron chelator with reported neuroprotective effects against stroke. Here, we aimed to explore the effects of deferoxamine on retinal hypoxia after SAH.
METHODS
SAH was established and deferoxamine was injected intraperitoneally for 3 days in the treatment group. To detect retinal new vessels, platelet endothelial cell adhesion molecule (CD31) was labeled by immunofluorescence and immunohistochemistry. Furthermore, the effects of deferoxamine on the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were revealed by western blot analysis.
RESULTS
The immunofluorescence and immunohistochemical staining of CD31 revealed a marked increase in new vessels in the retinal ganglion cell layer after deferoxamine treatment. By western blot analysis, HIF-1α and VEGF-A increased gradually in the first day and then rebounded to a new level on day 7. A deferoxamine-induced increase in HIF-1α/VEGF-A expression was also confirmed by western blot.
CONCLUSIONS
Our findings suggest that modulating the application of deferoxamine may offer therapeutic approaches to alleviate retinal complications after SAH.
背景与目的
蛛网膜下腔出血（SAH）与视网膜血管持续收缩有关，血管收缩导致视网膜缺血和缺氧。我们之前的研究结果还揭示了 SAH 后视网膜中与缺氧相关的元素的变化，进一步支持了 SAH 后视网膜血管痉挛和缺氧的假说。去铁胺是一种高亲和力的铁螯合剂，具有报道的对中风的神经保护作用。在这里，我们旨在探讨去铁胺对 SAH 后视网膜缺氧的影响。
方法
在治疗组中，建立了 SAH 模型，并腹腔内注射去铁胺 3 天。通过免疫荧光和免疫组织化学方法标记血小板内皮细胞黏附分子（CD31），以检测视网膜新生血管。此外，通过 Western blot 分析揭示了去铁胺对血管内皮生长因子 A（VEGF-A）和缺氧诱导因子-1α（HIF-1α）表达的影响。
结果
CD31 的免疫荧光和免疫组织化学染色显示，去铁胺处理后视网膜神经节细胞层中的新血管明显增加。通过 Western blot 分析，HIF-1α 和 VEGF-A 在第一天逐渐增加，然后在第 7 天反弹到新的水平。Western blot 还证实了去铁胺诱导的 HIF-1α/VEGF-A 表达增加。
结论
我们的研究结果表明，调节去铁胺的应用可能为缓解 SAH 后视网膜并发症提供治疗方法。
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