ω-3PUFAs对精神分裂症模型大鼠认知功能的影响

Effect of ω-3PUFAs on cognitive deficit in rats with schizophrenia

目的探讨ω-3PUFAs对MK-801诱导的精神分裂症（sz）大鼠认知功能损伤的拮抗作用及其机制。方法使用MK-801诱导大鼠精神分裂症模型；通过Morris水迷宫检测大鼠认知功能变化；应用Brdu染色检测大鼠海马新生神经元数量；通过Westonblot检测大鼠海马CREB、p-CREB、BDNF、TrkB、p-TrkB水平。结果MK-801引起大鼠精神分裂症样的认知功能障碍[水迷宫逃避潜伏期Ctr组为（6．51±3．10）s，Mod组为（15．27±6．20）s；穿过平台次数Ctr组（4．63±1．06）次，Mod组（2．00±1．15）次]、海马新生神经元数目减少（单位面积新生神经元数目相对水平Mod／Ctr为0．656±0．066）以及CREB／BDNF／TrkB通路损伤（灰度值相对水平Mod／Ctr：CREB为0．393±0．065，p-CREB为0．591±0．015。BDNF为0．716±0．115，TrkB为0．787±0．029，p-TrkB为0．586±0．013）；ω-3PUFAs通过增加CREB和TrkB水平及其磷酸化修饰、上调其活性而改善CREB／BDNF／TrkB通路（灰度值相对水平Pre／Ctr：CREB为1．139±0．111，p-CREB为0．845±0．243，BDNF为0．864±0．133，TrkB为0．916±0．022，p-TrkB为0．952±0．047）、恢复海马神经元数目（单位面积新生神经元数目相对水平Pre／Ctr为1．183±0．101），从而减轻精神分裂症大鼠认知功能障碍[水迷宫逃避潜伏期Pre组为（7．44±4．55）s；穿过平台次数Pre组为（3．86±1．68）次]。结论ω-3PUFAs可缓解MK-801造成的精神分裂症样认知功能损伤。

Objective To investigate the antagonistic effect of ω-3PUFAs on cognitive impairment in MK-801-induced schizophrenia （SZ） rats and its mechanism. Methods Rat model of schizophrenia was induced by MK-801. Morris water maze was used to detect the change of cognitive function in rats. The num- ber of neonatal neurons in hippocampus was detected by Brdu staining. CREB, p-CREB, BDNF, TrkB and p- TrkB levels were detected by Weston Blot. Results MK-801 induced schizophrenia-like cognitive impair- ment （the escape latency in the water maze test was （6.51±3.10）s for Ctr group, （15.27±6.20） s for Mod group ; acrossing times was （ 4.63± 1.06 ） times for Ctr group, （ 2.00± 1.15 ） times for Mod group ） , reduced the number of neonatal neurons in hippocampus （ the relative level of neonatal neuron number per unit area, Mod/Ctr was 0.656±0.066） and impaired the CREB/BDNF/TrkB pathway （the relative level of gray value, Mod/Ctr： CREB was 0.393±0.065, p-CREB was 0.591±0.015, BDNF was 0.716±0.115, TrkB was 0.787± 0.029 ,p-TrkB was 0.586±0.013）.ω-3PUFAs improved the CREB/BDNF/TrkB pathway activity by increas- ing CREB and TrKB level and their phosphorylation （the relative level of gray value, Pre/Ctr：CREB was 1.139±0.111, p-CREB was 0. 845 ± 0.243, BDNF was 0. 864± 0. 133, TrkB was 0.916± 0.022, p-TrkB was 0.952±0.047 ） , and then recovered the number of neonatal neurons in hippocampus （the relative level of neo- natal neuron number per unit area, Pre/Ctr was 1.183±0.101 ）, thereby reduced the cognitive dysfunction in schizophrenia rats（ the escape latency in the water maze was （7.44± 4.55 ） s for Pre; acrossing times was （3.86± 1.68） times for Pre）. Conclusion co-3PUFAs can relieve the MK-801-induced schizophrenia-like cognitive impaiIment.