Ma Kaizong, Langenbach Robert, Rapoport Stanley I, Basselin Mireille
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
J Lipid Res. 2007 Apr;48(4):848-54. doi: 10.1194/jlr.M600400-JLR200. Epub 2007 Jan 3.
Cyclooxygenase (COX)-2 plays an important role in brain arachidonic acid (20:4n-6) metabolism, and its expression is upregulated in animal models of neuroinflammation and excitotoxicity. Our hypothesis was that brain lipid composition would be altered in COX-2 knockout (COX-2(-/-)) compared with wild-type (COX-2(+/+)) mice, reflecting the important role of COX-2 in brain lipid metabolism. Concentrations of different lipids were measured in high-energy microwaved brain from COX-2(-/-) and COX-2(+/+) mice. Compared with the COX-2(+/+) mouse brain, the brain of the COX-2(-/-) mouse had a statistically significant 15% increase in phosphatidylserine (PtdSer) and significant 37, 27, and 32% reductions in triacylglycerol and cholesterol concentrations and in the cholesterol-to-phospholipid ratio, respectively. The normalized concentration of palmitic acid (16:0) was increased in PtdSer, as was the brain concentration of unesterified arachidic acid (20:0). A lifetime absence of COX-2 produces multiple changes in brain lipid composition. These changes may be related to reported changes in fatty acid kinetics and in resistance to neuroinflammation and excitotoxicity in the COX-2(-/-) mouse.
环氧化酶（COX）-2在脑花生四烯酸（20:4n-6）代谢中起重要作用，并且其表达在神经炎症和兴奋性毒性动物模型中上调。我们的假设是，与野生型（COX-2(+/+)）小鼠相比，COX-2基因敲除（COX-2(-/-)）小鼠的脑脂质组成会发生改变，这反映了COX-2在脑脂质代谢中的重要作用。测定了COX-2(-/-)和COX-2(+/+)小鼠高能微波处理脑内不同脂质的浓度。与COX-2(+/+)小鼠脑相比，COX-2(-/-)小鼠脑内磷脂酰丝氨酸（PtdSer）有统计学意义的15%升高，三酰甘油和胆固醇浓度以及胆固醇与磷脂比值分别有显著的37%、27%和32%降低。PtdSer中棕榈酸（16:0）的标准化浓度升高，未酯化花生酸（20:0）的脑浓度也升高。终生缺乏COX-2会导致脑脂质组成发生多种变化。这些变化可能与报道的COX-2(-/-)小鼠脂肪酸动力学变化以及对神经炎症和兴奋性毒性的抗性变化有关。
