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
刘丽霞 1王浩玉 1祁文秀1
作者信息
- 1. 山西医科大学汾阳学院,汾阳 032200
- 折叠
摘要
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Aβ142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.
Abstract
Objective:To investigate the expression changes of neuronal nitric oxide synthetase(nNOS)and α7 nic-otinic acetylcholine receptor(α7nAChR)in prefrontal cortex and hippocampus and the effects on the behavioral func-tions of Aβ induced dementia rats.Methods:Forty adult male Sprague-Dawley(SD)rats were intracerebroventricular-ly(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)and α7nAChR 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 and α7nAChR 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 criteri-on(P＜0.05 or P＜0.01),with significant increases of the protein expressions of nNOS and a7nAChR 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 and α7nAChR 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 and α7nAChR,and the improvement of the cognitive impairment in rats.There-fore,it is speculated that the synergistic effect of central nNOS and nicotine system is more beneficial to improving cog-nitive impairment function in dementia rats.
关键词
阿尔茨海默病/神经元型一氧化氮合酶/α7烟碱型乙酰胆碱受体/Y-迷宫/学习和记忆/大鼠Key words
Alzheimer's disease(AD)/neuronal nitric oxide synthetase(nNOS)/α7 nicotinic acetylcholine receptor(α7nAChR)/Y-maze/learning and memory/rat引用本文复制引用
基金项目
山西省自然科学基金(201801D121348)
山西医科大学汾阳学院科技发展重点研究项目(1304)
出版年
2024
NETL
NSTL
万方数据