丁苯酞对db/db小鼠学习记忆及海马NR2B受体的影响

目的 观察丁苯酞对2型糖尿病db/db小鼠学习记忆及海马N-甲基-D-天冬氨酸受体2B亚基(NR2B)表达的影响,探讨丁苯酞改善糖尿病认知功能障碍的机制.方法 将16只db/db小鼠按随机数字表法分为丁苯酞干预组(L-NBP组,n=8)和糖尿病对照组(DM组,n=8),同窝出生的db/m小鼠作为正常对照组(NC组,n=10).适应性喂养1周后,L-NBP组每日以溶于植物油中的丁苯酞灌胃,剂量为120 mg·kg-1,DM组与NC组则给予同等剂量的植物油灌胃,干预6周后,进行指标观察.应用Morris水迷宫检测小鼠的学习记忆能力.实时荧光定量PCR检测NR2B mRNA的表达情况.结果 与NC组比较,DM组小鼠逃避潜伏期延长和平均探索次数减少(P＜0.05),而L-NBP组小鼠较DM组上述学习记忆成绩明显改善(P＜0.05);与NC组相比,DM组和L-NBP组小鼠海马CA1区NR2B mRNA表达水平明显下降(P＜0.05),而L-NBP组较DM组NR2B mRNA表达水平明显增高(P＜0.05).结论 丁苯酞可改善糖尿病引发的认知功能障碍,推测其机制可能与上调海马NP,2B的表达有关.

Effect of L-3-n-butylphthalide on learning,memory and expression of NR2B receptors in hippocampus of db/db mice

Objective To study the effect of L-3-n-butylphthalide (L-NBP) on learning,memory and expression of N-Methyl-D-Aspartate (NMDA) receptor NR2B subunit of db/db mice and its possible mechanism.Methods Sixteen diabetic db/db mice were randomly assigned into two groups by random number table:L-NBP group (n =8) and DM group (n =8).Littermate db/m mice (NC group,n =10) were used as normal control.After one week of adaptive feeding the mice in L-NBP group were given L-NBP dissolved in vegetable oil by oral gavage once a day at a dose of 120 mg · kg-1 body weight,while DM and NC groups were both treated with equal amount of vegetable oil for 6 weeks.After 6 weeks of intervention,all the indexes were observed.The learning and memory ability of the mice was detected by Morris water maze test.The expression of NR2B mRNA was detected by realtime polymerase chain reaction(RTPCR).Results The escaping latency time(s) was longer and the average number of cross platform exploration was less in DM group than in NC group (P ＜ 0.05).The learning and memory scores were significantly higher in L-NBP group than in DM group (P ＜0.05).The expression levels of NR2B mRNA in hippocampal CA1 area were significantly lower in DM and L-NBP groups than in NC group (P ＜ 0.05).As compared with the mice in DM group,the expression levels of NR2B mRNA in hippocampal area were significantly higher in L-NBP group (P ＜ 0.05).Conclusions L-NBP can improve the learning and memory of db/db mice by up-regulating the expression of NR2B in hippocarnpal CA1 area.