Elevated CSF prostaglandin E2 levels in patients with probable AD
Elevated CSF prostaglandin E2 levels in patients with probable AD
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DOI：
10.1212/wnl.53.7.1495
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发表时间：
1999-10-22
期刊：
影响因子：
9.9
通讯作者：
Morrow, JD
中科院分区：
文献类型：
--
作者：
Montine, TJ;Sidell, KR;Morrow, JD
目的：测定AD患者和年龄匹配的对照者脑脊液中类花生酸浓度和脑环氧合酶活性。背景资料：非甾体类抗炎药可能通过抑制环加氧酶，从而减少CNS中前列腺素（PG）的产生或氧化应激，使AD患者受益。方法：CSF类花生酸和F-2-异前列烷（IsoP）水平测定在7个可能的AD患者和7个年龄匹配的对照组。环氧合酶活性测定微粒体从10个明确的AD患者和8个年龄匹配的对照组的海马。所有测量均使用气相色谱/质谱法进行。结果如下：在疑似AD患者中，CSF中前列腺素（PG）E-2浓度增加5倍（p < 0.01），6-酮-PGF（1 α）浓度降低4倍（p < 0.01）。在可能的AD患者中，总CSF类花生酸浓度没有变化。脑脊液F-2-IsoP是体内脂质过氧化的定量标志物，在疑似AD患者中增加（p < 0.05）。明确的AD患者海马中的环氧合酶活性与年龄匹配的对照组没有差异。结论：这些数据表明，环氧合酶活性可能不会显着促进中枢神经系统的氧化损伤在AD。可能的AD患者CSF PGE浓度增加表明，环氧合酶抑制剂可能通过限制PG产生而使AD患者受益。
Objective: To determine CSF eicosanoid concentrations and brain cyclo-oxygenase activity in AD patients and age-matched control subjects. Background: Nonsteroidal anti-inflammatory drugs may benefit AD patients by inhibiting cyclo-oxygenases and thereby reducing prostaglandin (PG) production or oxidant stress in the CNS. Methods: CSF eicosanoid and F-2-isoprostane (IsoP) levels were determined in seven probable AD patients and seven age-matched control subjects. Cyclo-oxygenase activity was determined in microsomes prepared from the hippocampus of 10 definite AD patients and 8 age-matched control subjects. All measurements were made using gas chromatography/mass spectrometry. Results: CSF concentrations of prostaglandin (PG) E-2 were increased fivefold (p < 0.01) and 6-keto-PGF(1 alpha) was decreased fourfold (p < 0.01) in probable AD patients. There was no change in total CSF eicosanoid concentration in probable AD patients. CSF F-2-IsoP, a quantitative marker of lipid peroxidation in vivo, was increased in probable AD patients (p < 0.05). Cyclo-oxygenase activity in the hippocampus from definite AD patients was not different from age-matched control subjects. Conclusions: These data suggest that cyclo-oxygenase activity may not contribute significantly to CNS oxidative damage in AD. Increased CSF PGE, concentration in probable AD patients suggest that cyclo-oxygenase inhibitors may benefit AD patients by limiting PG production.