左旋精氨酸和氯化胆碱改善Aβ1-42诱导的痴呆大鼠学习记忆能力

L-arginine and choline chloride improve the learning and memory abilities of Aβ1-42-induced dementia rats

目的:探讨中枢神经元型一氧化氮合酶(nNOS)和α7烟碱型乙酰胆碱受体(α7nAChR)在大鼠前额叶皮质和海马的表达变化以及对Aβ诱导的痴呆大鼠行为学的影响。方法:40只成年雄性SD大鼠均经侧脑室注射凝集态Aβ1-42制备痴呆模型,药物处理组分别注射一氧化氮(NO)前体左旋精氨酸(L-Arg)和(或)α7nAChR激动剂氯化胆碱(CC)。通过Y迷宫实验检测大鼠的空间学习和记忆功能,用免疫组织化学染色、Western Blot检测大鼠前额叶皮质和海马nNOS或α7nAChR的表达。结果:Aβ+L-Arg组或Aβ+CC组与Aβ+NS组比较,大鼠学习和记忆达标次数均减少(P<0.05或P<0.01),同时前额叶皮质和海马nNOS和α7nAChR表达均增加(P<0.05或P<0.01);与Aβ+L-Arg组或Aβ+CC组比较,联合用药的Aβ+L-Arg+CC组大鼠前额叶皮质和海马nNOS和α7nAChR表达水平均升高(P<0.05或P<0.01),同时学习和记忆达标次数均减少(P<0.05或P<0.01)。结论:侧脑室联合注入L-Arg和CC可明显提高二者在单独应用时对痴呆大鼠nNOS和α7nAChR表达的上调作用及认知功能障碍的改善效果。推测,中枢nNOS与烟碱系统的协同作用更有利于提高痴呆大鼠的认知功能。

Objective:To investigate the expression changes of neuronal nitric oxide synthetase(nNOS)andα7 nicotinic acetylcholine receptor(α7nAChR)in prefrontal cortex and hippocampus and the effects on the behavioral functions of Aβinduced dementia rats.Methods:Forty adult male Sprague-Dawley(SD)rats were intracerebroventricularly(i.c.v.)injected with condensed-amyloid beta peptides 1-42 to establish dementia model.Two drug treatment groups were respectively i.c.v.injected with the nitric oxide(NO)precursor L-arginine(L-Arg)andα7nAChR agonist choline chloride(CC),and another group were injected with them both.Spatial learning and memory functions of rats were evaluated by Y-maze experiment.The expressions of nNOS andα7nAChR in prefrontal cortex and hippocampus were measured by immunohistochemical staining and Western Blot.Results:The results showed that,in comparison with Aβ+NS group,rats in Aβ+L-Arg group or Aβ+CC group exhibited decreases in the numbers to reach the criterion(P<0.05 or P<0.01),with significant increases of the protein expressions of nNOS andα7nAChR in prefrontal cortex and hippocampus(P<0.05 or P<0.01).However,compared with Aβ+L-Arg group or Aβ+CC group,the protein expressions of nNOS andα7nAChR in prefrontal cortex and hippocampus of rats were significantly increased(P<0.05 or P<0.01),and the numbers to reach the criterion were decreased in Aβ+L-Arg+CC group(P<0.05 or P<0.01).Conclusion:The combined use of L-Arg and CC in the lateral ventricle can significantly enhance the effects of either on the up-regulation of nNOS andα7nAChR,and the improvement of the cognitive impairment in rats.Therefore,it is speculated that the synergistic effect of central nNOS and nicotine system is more beneficial to improving cognitive impairment function in dementia rats.