Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, Taiwan.
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan.
Int J Mol Sci. 2022 Feb 14;23(4):2095. doi: 10.3390/ijms23042095.
Clinically, acute ischemic symptoms in the eyes are one of the main causes of vision loss, with the associated inflammatory response and oxidative stress being the key factors that cause injury. Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common type of ischemic optic neuropathy (ION); however, there are still no effective or safe treatment options to date. In this study, we investigated the neuroprotective effects of n-butylidenephthalide (BP) treatment in an experimental NAION rodent model (rAION). BP (10 mg/kg) or PBS (control group) were administered on seven consecutive days in the rAION model. Rats were evaluated for visual function by flash visual evoked potentials (FVEPs) at 4 weeks after NAION induction. The retina and optic nerve were removed for histological examination after the rats were euthanized. The molecular machinery of BP treatment in the rAION model was analyzed using Western blotting. We discovered that BP effectively improves retinal ganglion cell survival rates by preventing apoptotic processes after AION induction and reducing the inflammatory response through which blood-borne macrophages infiltrate the optic nerve. In addition, BP significantly preserved the integrity of the myelin sheath in the rAION model, demonstrating that BP can prevent the development of demyelination. Our immunoblotting results revealed the molecular mechanism through which BP mitigates the neuroinflammatory response through inhibition of the NF-κB signaling pathway. Taken together, these results demonstrate that BP can be used as an exceptional neuroprotective agent for ischemic injury.
临床上,眼部急性缺血症状是导致视力丧失的主要原因之一,相关的炎症反应和氧化应激是导致损伤的关键因素。非动脉炎性前部缺血性视神经病变(NAION)是最常见的缺血性视神经病变(ION)类型;然而,迄今为止,仍然没有有效的或安全的治疗方法。在这项研究中,我们研究了丁烯基苯酞(BP)在实验性 NAION 啮齿动物模型(rAION)中的神经保护作用。在 rAION 模型中,连续 7 天给予 BP(10mg/kg)或 PBS(对照组)。在 NAION 诱导后 4 周,通过闪光视觉诱发电位(FVEPs)评估大鼠的视觉功能。在大鼠安乐死后,取出视网膜和视神经进行组织学检查。使用 Western blot 分析 BP 治疗 rAION 模型的分子机制。我们发现,BP 通过防止 AION 诱导后细胞凋亡过程和减少血源性巨噬细胞浸润视神经的炎症反应,有效提高了视网膜神经节细胞的存活率。此外,BP 显著保留了 rAION 模型中髓鞘的完整性,表明 BP 可以防止脱髓鞘的发生。我们的免疫印迹结果揭示了 BP 通过抑制 NF-κB 信号通路减轻神经炎症反应的分子机制。综上所述,这些结果表明 BP 可用作缺血性损伤的一种特殊神经保护剂。