二十二碳六烯酸对1-溴丙烷致大鼠学习能力损伤的拮抗作用

Antagonistic effect of docosahexaenoic acid on damaged learning ability induced by 1-bromopropane in rats

目的观察二十二碳六烯酸（DHA）对1-溴丙烷（1-BP）致大鼠学习能力损伤的拮抗作用。方法将48只健康成年SPF级雄性Wistar大鼠随机分为4组，即对照（玉米油）组、1-BP染毒组和低、高剂量DHA干预组，每组12只。1-BP染毒组和低、高剂量DHA干预组每天灌胃染毒800mg／kg的1-BP；4h后，低、高剂量DHA干预组分别灌胃染毒250、500mg，kg的DHA，每日1次，连续11d。染毒第8～11天采用Moms水迷宫试验中的定位导航试验检测大鼠的学习能力。染毒结束后，检测大脑皮层匀浆中还原型谷胱甘肽（GSH）、丙二醛（MDA）含量及谷胱甘肽还原酶（GR）活力。采用Westemblotting方法检测大脑皮层脑红蛋白（neuroglobin，Ngb）的表达。结果与对照组比较，1-BP染毒组大鼠游泳总路程和逃避潜伏期延长（P〈0．05）；与1-BP染毒组相比，各剂量DHA干预组大鼠的游泳路程和逃避潜伏期缩短（P〈0．05）。与对照组比较，1—BP染毒组大鼠大脑皮层匀浆中GSH含量及GR活力均下降，而1-BP染毒组MDA含量及高剂量DHA干预组GSH含量均升高（P〈0．05）；与1-BP染毒组比较，各剂量DHA干预组大鼠大脑皮层匀浆中GSH含量及GR活力均升高，MDA含量均下降（P〈0．05）。与对照组比较，1-BP染毒组和低剂量DHA干预组大鼠大脑皮层匀浆中Ngb蛋白的表达水平均下降，而高剂量DHA干预组N曲蛋白的表达水平升高（P〈0．05）；与1-BP染毒组比较，各剂量DHA干预组大鼠大脑皮层匀浆中Ngb蛋白的表达水平均升高（P〈0．05）o结论DHA能够减轻1-BP导致的大鼠中枢神经系统氧化应激反应及由此引起的学习能力损伤，激活GR活力、增强Ngb表达可能是DHA的保护机制之-。

Objective To investigate the antagonistic effects of docosahexaenoic acid （DHA） on the damage of learning abilities induced by 1-bromopropane （1-BP） in rats. Methods Forty-eight male Wistar rats were randomly divided into four groups, 12 in each, such as control group, I-BP group（800 mg/kg body weight）, DHA（250 mg/kg body weight）＋l-BP（800 mg/kg body weight） group and DHA （500 mg/kg body weight）＋l-BP （800 mg/kg body weight） group. The rats in each group were treated with 1-BP and DHA though gavage for 11 consecutive days; The animals in control group were given equal volume coin oil. During the 8th-llth day of exposure,the Morris water maze was applied to test animals＇ learning ability. After Morris water maze test,the rats cerebral cortex were collected to detect glutathione （GSH） and malondialdehyde （MDA） contents,and glutathione reductase （GR） respectively. The protein expression level of neuroglobin （Ngb） in the cerebral cortex was analyzed by western blotting method. Results Compared with the control group, the escape latency and swim distance of rats in 1-BP group were significantly prolonged （P〈0.05）,while the latency and swim distance of rats treated with DHA at 250 mg/kg body weight and 500 mg/kg body weight were much less（P〈0.05）, and GSH contents significandy decreased, MDA content increased in 1-BP group. Compared with 1-BP group,250 mg/kg body weight and 500 mg/kg body weight DHA treatment could signifieandy upregulate the GSH and decrease the MDA levels （P〈0.05）. 1-BP exposure also resulted in the decrease of GR activities （P〈0.05）,however DHA administration could increase the GR activity,compared with 1-BP group （P〈0.05）. Compared with control group, the expression of Ngb in 1-BP group was significantly decreased （P〈0.05）, while in 250 mg/kg body weight and 500 mg/kg body weight DHA could significantly unregulate the expression of Ngb. Conclusion DHA has the antagonistic effects on the damage of learning abilities due to oxidative stress induced by 1-BP,and the increase of GSH and elevation of GR activities may be one of key mechanisms among rats.