L-NMMA对阿尔茨海默病模型大鼠海马齿状回区谷氨酸含量的影响

Effect of L-NMMA on glutamate levels in the hippocampal dentate gyrus in a rat model of Alzheimer's disease

目的观察一氧化氮(NO)合成酶抑制剂L-单甲基-精氨酸(L-NMMA)对阿尔茨海默病(AD)模型大鼠的海马齿状回(DG)区的谷氨酸(Glu)含量,以及对其空间学习记忆能力的影响。方法 18只雌性SD大鼠随机分为sham组、AD组、L-NMMA组,每组6只。AD组和L-NMMA组应用双侧卵巢摘除术结合腹腔注射D-半乳糖法制备AD模型,之后在每次Morris水迷宫(MWM)训练前向L-NMMA组腹腔注射L-NMMA。利用高效液相色谱分析法及脑部微量透析法,检测大鼠海马DG区Glu的含量,通过MWM检测大鼠的空间学习记忆能力。向大鼠DG区注射L-NMMA,观察其对AD大鼠的学习记忆行为及大鼠DG区Glu含量的影响。结果 3组大鼠Glu的基础含量差异无统计学意义(均P>0.05)。AD组逃避潜伏期显著延长,AD组穿越原平台区次数明显减少(均P<0.05);L-NMMA组与AD组比较穿越原站台区的次数明显增加,逃避潜伏期明显缩短,大鼠空间学习记忆能力明显改善(均P<0.05)。sham组和L-NMMA组Glu含量,在训练的第2、3天明显增加(均P<0.05),其后又回到训练前水平;AD组Glu含量在训练过程中均明显增加(均P<0.05)。结论 L-NMMA可通过恢复空间学习过程中的海马DG区Glu的反应,改善AD大鼠的空间学习记忆功能。

Objective To observe the effect of an inhibitor of nitric oxide synthase L-NMMA on glutamate （Glu） levels in the hipp- ocampal dentate gyms （DG） during spatial learning in a rat model of Alzheimer＇s disease （AD）. Methods 18 female Sprague-Dawley rats were divided into sham, AD and L-NMMA groups, 6 rats in every group. The extracellular concentration of Glu in the DG was determined by in vivo microdialysis and HPLC, and the spatial learning and memory abilities were detected by Morris water maze （MWM）. The effects of microinjection of L-NMMA into the DG in spatial learning and memory and Glu levels in the DG were demonstrated in AD rats. Results There were no significant differences of the Glu basal levels in extracellular fluid of hippocampal DG between the three groups（ P 〉0.05, re- spectively）. In the MWM test, the escape latency of rats in AD group was significantly prolonged, and the number of rats in AD group was also significantly reduced （ all P 〈0.05 ）. In the MWM test, Glu levels in the DG regions of sham and AD ＋ L-NMMA groups were increased significantly on days 2 and 3 of training （ all P 〈 0.05 ） and then returned to pre-training levels ; whereas Glu levels of AD group in the train- ing process were significantly increased （all P 〈 0.05）. Conclusions L-NMMA in the hippocampal DG improves the spatial learning and memory impairment in AD rats, in part by recovering the responses of Glu in the DG during spatial learning.