Wang Hai-Yan, Wang Yi, Zhang Yuan, Wang Jing, Xiong Shu-Yu, Sun Qian
Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Jiaotong University, Shanghai 200080, China.
Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai 200080, China.
Int J Ophthalmol. 2018 May 18;11(5):736-746. doi: 10.18240/ijo.2018.05.05. eCollection 2018.
To explore the roles of phospholipids and sphingolipids in the inflammatory process of uveitis.
Aqueous humor (AH) and the retina were obtained from endotoxin-induced uveitis (EIU) rats during the acute inflammation stage (24h after endotoxin injection). Lipids were extracted using a modified Bligh and Dyer method and subjected to mass spectrometric identification using class-specific lipid standards and ratiometric quantification. Relative intensity analysis was performed to evaluate the amount change of common lipids between the EIU and control groups.
Unique lipid species encompassing all five phospholipid classes were found in both control and the EIU AH and retina. Commensurate with the significantly increased level of lysophospholipids in the EIU AH and retina, we found that the ratio of lysophospholipids to total phospholipids was significantly increased too. We also detected a significant increase in 18:0 lysophosphatidylcholine levels in the EIU group (fold change =6.4 in AH and 3.8 in retina). Cer240, Cer241, and SM240 levels remarkably increased in the EIU AH. Enhanced C12 ceramide-1-phosphate (C12 C-1-P), C16 C-1-P, C24 C-1-P, and upregulated Cer160, Cer240, SM120, and SM240 were found in EIU retina. C-1-P was believed to restore homeostasis by inhibiting nuclear factor kappa B (NF-κB) activation. However, we still found elevated NF-κB levels in the EIU retina.
A variety of lipids might have played a critical role in EIU inflammation. Exogenous topical application of these protective lipids or inhibition of these pro-inflammatory lipids may be useful therapeutic strategies for the resolution of EIU.
探讨磷脂和鞘脂在葡萄膜炎炎症过程中的作用。
在内毒素诱导的葡萄膜炎（EIU）大鼠急性炎症期（内毒素注射后24小时）获取房水（AH）和视网膜。采用改良的布利格和戴尔法提取脂质，并使用特定类别的脂质标准品进行质谱鉴定和比例定量。进行相对强度分析以评估EIU组和对照组之间常见脂质的含量变化。
在对照组和EIU组的AH及视网膜中均发现了涵盖所有五种磷脂类别的独特脂质种类。与EIU组AH和视网膜中溶血磷脂水平显著升高相一致，我们发现溶血磷脂与总磷脂的比例也显著增加。我们还检测到EIU组中18:0溶血磷脂酰胆碱水平显著升高（AH中变化倍数为6.4，视网膜中为3.8）。EIU组AH中Cer240、Cer241和SM240水平显著升高。在EIU视网膜中发现C12神经酰胺-1-磷酸（C12 C-1-P）、C16 C-1-P、C24 C-1-P增强，以及Cer160、Cer240、SM120和SM240上调。C-1-P被认为通过抑制核因子κB（NF-κB）激活来恢复体内平衡。然而，我们仍发现EIU视网膜中NF-κB水平升高。
多种脂质可能在EIU炎症中起关键作用。外源性局部应用这些保护性脂质或抑制这些促炎脂质可能是解决EIU的有用治疗策略。
