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ω-3多不饱和脂肪酸在前部缺血性视神经病变大鼠模型中的神经保护作用

Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.

作者信息

Georgiou Tassos, Wen Yao-Tseng, Chang Chung-Hsing, Kolovos Panagiotis, Kalogerou Maria, Prokopiou Ekatherine, Neokleous Anastasia, Huang Chin-Te, Tsai Rong-Kung

机构信息

Ophthalmos Research and Educational Institute, Nicosia, Cyprus.

Institute of Eye Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.

出版信息

Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1603-1611. doi: 10.1167/iovs.16-20979.

Abstract

PURPOSE

The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION).

METHODS

The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects.

RESULTS

Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group.

CONCLUSIONS

The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.

摘要

目的

本研究旨在探讨ω-3多不饱和脂肪酸(ω-3 PUFA)给药对大鼠前部缺血性视神经病变(rAION)模型的治疗效果。

方法

测量血液中花生四烯酸/二十碳五烯酸(AA/EPA)水平以确定建议剂量。对诱导出rAION的大鼠连续10天每日经口灌胃给予鱼油(1克/天EPA)或磷酸盐缓冲盐水(PBS),以评估神经保护作用。

结果

血液脂肪酸分析显示,鱼油治疗10天后,AA/EPA比值从17.6降至≤1.5。与PBS治疗组相比,ω-3 PUFA治疗组的视网膜神经节细胞(RGC)密度和闪光视觉诱发电位(FVEP)的P1-N2波幅显著更高(P<0.05)。与PBS治疗的大鼠相比,ω-3 PUFA治疗的大鼠RGC层中的凋亡细胞数量显著减少(P<0.05)。在rAION模型中,ω-3 PUFAs治疗使视神经(ON)处的巨噬细胞募集减少了3.17倍。与PBS治疗组相比,ω-3 PUFA治疗组诱导产生了减少炎症的M2巨噬细胞标志物。此外,ω-3 PUFA治疗组中肿瘤坏死因子-α、白细胞介素-1β和诱导型一氧化氮合酶的mRNA水平显著降低。

结论

给予ω-3 PUFAs对rAION具有神经保护作用,可能是通过RGC抗凋亡和减少炎症细胞浸润的抗炎双重作用,以及调节巨噬细胞极化以减少细胞因子诱导的视神经损伤来实现的。

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