Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
Neurochem Int. 2010 Mar;56(4):585-9. doi: 10.1016/j.neuint.2009.12.022. Epub 2010 Jan 12.
Neuroinflammation is believed to play an important role in neurological diseases such as Alzheimer's disease (AD). Growing evidence suggests that n-3 PUFA have protective effects by inhibiting inflammatory processes including synthesis of eicosanoids from arachidonic acid. There is also some evidence suggesting that inflammatory mediators associated with the arachidonic acid cascade may be modulated by n-3 PUFA in healthy animals. Therefore, in this study, the effect of n-3 PUFA on brain cortex fatty acid composition, and on the expression of calcium-dependant cytosolic phospholipase A(2) (cPLA(2)) and cyclooxygenase-2 (COX-2) was assessed in the transgenic fat-1 mouse. Phospholipid fatty acid composition was determined by thin layer and gas chromatography, while cortical cPLA(2) and COX-2 were determined by Western blotting. 22:6 n-3 levels were up to 220% higher while n-6 PUFA levels were up to 77% lower in fat-1 phospholipid fractions of the cortex as compared to wildtype (WT) mice. COX-2 protein levels were 25% lower in fat-1 as compared to WT mice (p=0.02), but cPLA(2) expression levels did not change. Our results suggest that this model could be used to investigate mechanisms by which n-3 PUFA regulate neuroinflammation.
神经炎症被认为在神经退行性疾病（如阿尔茨海默病）中发挥重要作用。越来越多的证据表明，n-3PUFA 通过抑制包括花生四烯酸合成类二十烷酸在内的炎症过程发挥保护作用。还有一些证据表明，与花生四烯酸级联相关的炎症介质可能在健康动物中被 n-3PUFA 调节。因此，在本研究中，我们评估了 n-3PUFA 对转基因 fat-1 小鼠大脑皮质脂肪酸组成的影响，以及对钙依赖性细胞质磷脂酶 A2（cPLA2）和环氧化酶-2（COX-2）表达的影响。通过薄层和气相色谱法测定磷脂脂肪酸组成，通过 Western 印迹法测定皮质 cPLA2 和 COX-2。与野生型（WT）小鼠相比，fat-1 大脑皮质的 22:6n-3 水平高达 220%，而 n-6PUFA 水平低至 77%。与 WT 小鼠相比，fat-1 小鼠的 COX-2 蛋白水平低 25%（p=0.02），但 cPLA2 表达水平没有变化。我们的结果表明，该模型可用于研究 n-3PUFA 调节神经炎症的机制。
