Wang Ze-Jian, Li Guang-Mei, Nie Bao-Ming, Lu Yang, Yin Ming
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.
Chem Biol Interact. 2006 Mar 10;160(1):80-7. doi: 10.1016/j.cbi.2005.12.008. Epub 2006 Jan 31.
Stearic acid is a long-chain saturated fatty acid consisting of 18 carbon atoms without double bonds. In the present study, we reported the neuroprotective effects and mechanism of stearic acid on cortical or hippocampal slices insulted by oxygen-glucose deprivation, NMDA or hydrogen peroxide (H(2)O(2)) in vitro. Different types of models of brain slice injury in vitro were developed by 10 min of oxygen/glucose deprivation, 0.5 mM NMDA or 2 mM H(2)O(2), respectively. After 30 min of preincubation with stearic acid (3-30 microM), cortical or hippocampal slices were subjected to oxygen-glucose deprivation, NMDA or H(2)O(2). Then the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride (TTC) method. Population spikes were recorded in randomly selected hippocampal slices. Stearic acid (3-30 microM) dose-dependently protected brain slices from oxygen-glucose deprivation, NMDA and H(2)O(2) insults. Its neuroprotective effect against H(2)O(2) insults can be completely blocked by wortmannin (inhibitor of PI3K) and partially blocked by H7 (inhibitor of PKC) or genistein (inhibitor of TPK). Treatment of cortical or hippocampal slices with 30 microM stearic acid resulted in a significant increase in PI3K activity at 5, 10, 30 and 60 min. These observations reveal that stearic acid can protect cortical or hippocampal slices against injury induced by oxygen-glucose deprivation, NMDA or H(2)O(2), and its neuroprotective effects are via phosphatidylinositol 3-kinase dependent mechanism.
硬脂酸是一种由18个碳原子组成的无双键的长链饱和脂肪酸。在本研究中，我们报道了硬脂酸对体外氧糖剥夺、NMDA或过氧化氢（H₂O₂）损伤的皮质或海马切片的神经保护作用及其机制。分别通过10分钟的氧/糖剥夺、0.5 mM NMDA或2 mM H₂O₂建立了不同类型的体外脑切片损伤模型。在用硬脂酸（3 - 30 μM）预孵育30分钟后，将皮质或海马切片进行氧糖剥夺、NMDA或H₂O₂处理。然后使用氯化三苯基四氮唑（TTC）法评估组织活性。在随机选择的海马切片中记录群体峰电位。硬脂酸（3 - 30 μM）剂量依赖性地保护脑切片免受氧糖剥夺、NMDA和H₂O₂损伤。其对H₂O₂损伤的神经保护作用可被渥曼青霉素（PI3K抑制剂）完全阻断，被H7（PKC抑制剂）或染料木黄酮（TPK抑制剂）部分阻断。用30 μM硬脂酸处理皮质或海马切片导致PI3K活性在5、10、30和60分钟时显著增加。这些观察结果表明，硬脂酸可以保护皮质或海马切片免受氧糖剥夺、NMDA或H₂O₂诱导的损伤，并且其神经保护作用是通过磷脂酰肌醇3 - 激酶依赖性机制实现的。
