Objective To investigate the protective effects ofdocosahexaenoic acid (DHA) and nervonic acid (NA) on the learning and memory abilities in rats exposed to 1-bromopropane (1-BP) and their action mechanisms.Methods Forty male Wister rats (specific pathogen-free) were randomly divided into 4 groups (n=10 for each),i.e.,solvent control group,1-BP (800 mg/kg) group,NA (150 mg/kg)+1-BP (800 mg/kg) group,and DHA (500 mg/kg)+1-BP (800 mg/kg) group.The rats were given respective test substances by gavage for 7 d.The Morris water maze (MWM) test was performed from days 8 to 12 to evaluate the rats' learning and memory abilities.After MWM test,rats were sacrificed in the next day,and cerebral cortex was quickly dissected and homogenized in an ice bath.The supernatant of the obtained homogenate was collected to measure the content of glutathione (GSH) and malondialdehyde (MDA) and the activities of glutathione reductase (GR) and γ-glutamate cysteine ligase (γ-GCL).Results The MWM spatial navigation test showed that the 1-BP group had significantly longer escape latency and significantly longer total swimming distance compared with the control group (P＜0.05),while the DHA+1-BP group had significant decreases in escape latency and total swimming distance compared with the 1-BP group (P＜0.05).The spatial probe test showed that the number of platform crossings was significantly greater in the DHA+1-BP group and NA+1-BP group than in the 1-BP group (P＜0.05); compared with the control group,the 1-BP group had a significantly lower ratio of time spent in the zone around the platform to total time (P＜0.05),and the ratio was significantly higher in the DHA+1-BP group than in the 1-BP group (P＜0.05).Compared with the control group,the 1-BP group had a 18.1％ decrease in GSH content,and DHA could significantly reverse 1-BP-induced decrease in GSH content (P＜0.05).Compared with the 1-BP group,the DHA+1-BP group and NA+1-BP group had significantly decreased MDA content (P＜0.05),the DHA+1-BP group had significantly increased GR activity (P＜0.05),and the NA+1-BP group had significantly increased γ-GCL activity (P＜0.05).Conclusion The rats exposed to 1-BP have oxidative stress in the brain and impaired cognitive function.DHA and NA can reduce 1-BP-induced cognitive function impairment in rats,possibly by increasing the activities of GR and γ-GCL and the content of GSH in the brain.%目的 观察二十二碳六烯酸(docosahexaenoic acid,DHA)和神经酸(nervonic acid)对1-溴丙烷(1-bromopropane,1-BP)致大鼠学习认知功能损伤的保护作用及机制.方法 SPF级雄性Wistar大鼠40只,随机分为溶剂对照组、1-BP染毒组(800 mg/kg)、神经酸(150 mg/kg)+ 1-BP组(800 mg/kg)、DHA(500mg/kg)+1-BP组(800 mg/kg),每组10只.分别经灌胃给予相应受试物7d,第8天开始采用Morris水迷宫试验检测大鼠的学习和记忆能力,连续5d.水迷宫结束次日断头处死大鼠,迅速剥离大鼠大脑皮层,在冰浴中制备组织匀浆,分别测定还原型谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)含量、谷胱甘肽还原酶(glutathione reductase,GR)及γ-谷氨酰半胱氨酸连接酶(γ-glutamate cysteineligase,γ-GCL)活力.结果 Morris水迷宫定位航行试验中,1-BP染毒组大鼠的逃避潜伏期和游泳总路程明显高于对照组,差异有统计学意义(P＜0.05);与1-BP染毒组比较,DHA+1-BP组大鼠的逃避潜伏期和游泳总路程明显降低,差异有统计学意义(P＜0.05).空间探索试验中,与1-BP组比较,DHA+1-BP组和神经酸+1-BP组的穿越平台次数明显增加,差异均有统计学意义(P＜0.05).与对照组比较,1-BP染毒组平台周边时间/总时间比值明显减少,与1-BP组比较,DHA+1-BP组动物的平台周边时间/总时间比值明显增加,差异均有统计学意义(P＜0.05).与对照组比较,1-BP染毒组动物大脑GSH含量降低了18.1％,DHA+1-BP组GSH含量明显高于1-BP组,差异均有统计学意义(P＜0.01).与1-BP染毒组比较,DHA+1-BP组和神经酸+1-BP组MDA含量明显降低,DHA+1-BP组GR酶活力明显增加,神经酸+1-BP组γ-GCL酶活力明显升高,差异均有统计学意义(P＜0.05).结论 1-BP染毒导致大鼠大脑氧化应激,损伤认知功能;DHA和神经酸在一定程度上可减轻1-BP对大鼠认知功能的损伤;增强GR和γ-GCL酶活力,升高大脑GSH含量,可能是其作用机制之一.
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