一氧化氮对大鼠学习记忆和胆碱能系统的影响  

The effects of nitric oxide on spatial learning-memory and cholinergic system in rats

作　　者：杨伟[1] 未小明 荆治华[1] 赵建强[3] 刘丽霞[3] 祁文秀[3] 

机构地区：[1]山西医科大学 [2]河南南阳医学院生理学教研室 [3]山西医科大学汾阳学院生理学教研室

出　　处：《神经解剖学杂志》2013年第2期166-172,共7页Chinese Journal of Neuroanatomy

基　　金：山西省大学生创新实验基金资助项目(2009103)

摘　　要：目的:探讨一氧化氮(nitric oxide,NO)在大鼠空间学习和记忆过程中的作用及其对胆碱能受体作用机制。方法:大鼠侧脑室分别注射NO前体左旋精氨酸(L-arginine,L-Arg,L-Arg组)、α7烟碱型乙酰胆碱受体(α7nicotinic acetylcholine receptor,α7nAChR)拮抗剂甲基牛扁亭(methyllycaconitine,MLA,MLA组)、α7nAChR激动剂氯化胆碱(choline chloride,CC组)、一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯(nω-nitro-L-arginine methylester,L-NAME,L-NAME组)以及先注射MLA再注射L-Arg(ML组)、先注射L-NAME再注射氯化胆碱(NC组),并以等量生理盐水(NS组)作为对照。用Y型迷宫刺激器、硝酸还原酶法、免疫组织化学以及Western-Blot等技术分别检测大鼠空间学习和记忆行为能力、大脑皮质和海马NO含量和α7nAChR的表达。结果:与对照组比较,Y迷宫空间学习能力达标次数和24 h后30次测试记忆行为中错误反应次数在L-Arg组和CC组均减少,而在MLA组和L-NAME组均增多;大脑前额叶皮质和海马NO含量和α7nAChR阳性细胞数以及蛋白含量在L-Arg组和CC组均明显增多,而在MLA组和L-NAME组均明显减少。ML组和NC组分别与L-Arg和CC组相比较,大鼠学习和记忆行为能力均明显减弱,并且大脑前额叶皮质和海马NO含量以及α7nAChR的表达均减少。结论:侧脑室应用MLA或L-NAME可减弱L-Arg或氯化胆碱对大鼠空间学习和记忆行为能力的促进作用;NO通过α7nAChR促进大鼠空间学习和记忆能力。Objective：To explore the effects of nitric oxide （NO） on spatial learning and memory in rats and its cholinergic receptor mechanisms. Methods： L-arginine （L-Arg, a nitric oxide precursor）, methyllycaconitine （MLA, an antagonist of ct7 nicotinic acetylcholine receptor （c^7nAChR））, choline chloride （CC, an agonist of otynAChR） , Nω-nitro- L-arginine methyl ester （L-NAME, a nitric oxide synthase inhibitor） was injected into rat cerebral lateral ventricles, respectively. Additionally, two mgre groups were Ms wsed. MLA was intracerebroventricularly injected first and followed by the administration of L-Arg, and L-NAME injected first follwed by choline chloride. The same amount of normal saline was used as control. The spatial learning and memory was studied with Y maze test. The level of NO in frontal cortex and hippocampus was measured by nitrate reductase assay, aTnAChR expression was determined by immunobistochemistry or Western Blot. Results： Compared with control group, the frequency that the rats reached the learning standard and that the rats reacted with error within 30 memorv measurements after 24 hours decreased in L-Are re＇out） and CC Tounp whileincreased in MLA group and L-NAME group; The NO level, the number of ct7 nAChR positive cells and ctTnAChR protein level in prefrontal cortex and hippocampus significantly increased in L-Arg group and CC group, while decreased in MLA group and L-NAME group. The ability of learning and memory significantly weakened in ML group and NC group, com- pared with L-Arg group and CC group. Moreover, the NO level and expressions of o^TnAChR reduced in prefrontal cortex and hippocampus. Conclusion： Intracerebroventricular administration of MLA or L-NAME impaired the ability of L-Arg or choline chloride to enhance spatial learning and memory in rats. NO enhanced spatial learning and memory via ct7 nAChR.

关 键 词：一氧化氮 左旋精氨酸 Nω-硝基-L-精氨酸甲酯 α7 烟碱型乙酰胆碱受体 甲基牛扁亭 氯化胆碱 Y-迷宫 学习记忆 

分 类 号：R965[医药卫生—药理学]