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一氧化氮和烟碱型乙酰胆碱受体在大鼠学习记忆中的联合作用

荆治华, 未小明, 王少虎, 陈宇飞, 刘丽霞, 祁文秀

山西医科大学，太原 030001；南阳医学高等专科学校生理学教研室，南阳 473061；山西医科大学汾阳学院生理学教研室，汾阳 032200

摘要

本文旨在探讨一氧化氮(NO)和烟碱型乙酰胆碱受体(nicotinic acetylcholine receptor, nAChR)在大鼠学习记忆过程中的相互作用。大鼠侧脑室注射NO前体左旋精氨酸(L-Arg)(L-Arg组)或α7nAChR激动剂氯化胆碱(choline chloride，CC组)，以及联合注射L-Arg和氯化胆碱(L-Arg+CC组)，和先给予α7nAChR拮抗剂甲基牛扁亭(methyllycaconitine, MLA)再联合注射L-Arg和氯化胆碱(MLA+L-Arg+CC组)、先给一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME)再联合注射L-Arg和氯化胆碱(L-NAME+L-Arg+CC组)，侧脑室注射生理盐水(NS组)作为对照。用Y型迷宫刺激器检测大鼠的学习和记忆行为能力；用NO试剂盒、免疫组织化学和Western blot分别检测大鼠海马NO含量和α7nAChR及神经元型一氧化氮合酶(neuronal nitric oxide synthase, nNOS)的表达。结果显示，L-Arg+CC组与L-Arg或CC组比较，Y迷宫学习和记忆行为能力均明显增强，同时大鼠海马NO含量、nNOS和α7nAChR表达的光密度值均明显增多；而MLA+L-Arg+CC或L-NAME+L-Arg+CC组与L-Arg+CC组相比较，大鼠学习和记忆行为能力明显减弱，并且海马NO含量及nNOS和α7nAChR的表达均降低。以上结果表明，侧脑室联合应用L-Arg和氯化胆碱可明显提高其单独应用时的大鼠海马NO含量及nNOS和α7nAChR表达，并增强大鼠学习和记忆行为能力；而提前阻断α7nAChR或抑制nNOS后，其联合应用L-Arg和氯化胆碱的效应也得到了抑制。因此推测，NO和nAChR在学习记忆中可能存在着相互协同作用。

关键词： 一氧化氮; α7烟碱型乙酰胆碱受体; 左旋精氨酸; 氯化胆碱; 协同作用; Y-迷宫; 学习记忆

分类号：R338

[The synergetic effects of nitric oxide and nicotinic acetylcholine receptor on learning and memory of rats.] [Article in Chinese]

JING Zhi-Hua, WEI Xiao-Ming, WANG Shao-Hu, CHEN Yu-Fen, LIU Li-Xia, QI Wen-Xiu

Shanxi Medical University, Taiyuan 030001, China； Department of Physiology, NanYang Medical College, Nanyang 473061 , China； Department of Physiology, Fenyang College of Shanxi Medical University, Fenyang 032200, China

Abstract

The aim of the present study is to explore the interaction of nitric oxide (NO) and nicotinic acetylcholine receptor (nAChR) on learning and memory of rats. Rats were intracerebroventricularly (i.c.v.) injected with L-arginine (L-Arg, the NO precursor) (L-Arg group) or choline chloride (CC, an agonist of α₇nAChR) (CC group), and with combined injection of L-Arg and CC (L-Arg+CC group), and methyllycaconitine (MLA, α₇nAChR antagonist) or N^ω-nitro-L-arginine methylester (L-NAME, nitric oxide synthase inhibitor) i.c.v. injected first and followed by administration of L-Arg combined with CC (MLA+L-Arg+CC group or L-NAME+L-Arg+CC group), respectively, and normal saline was used as control (NS group). The learning and memory ability of rats was tested with Y-maze; the level of NO and the expressions of neuronal nitric oxide synthase (nNOS) or α₇nAChR in hippocampus were measured by NO assay kit, immunohistochemistry or Western blot. The results showed that compared with L-Arg group or CC group, the rats' learning and memory behavioral ability in Y-maze was observably enhanced and the level of NO, the optical density of nNOS-like immunoreactivity (LI) or α₇nAChR-LI in hippocampus were significantly increased in L-Arg+CC group; Compared with L-Arg+CC group, the ability of learning and memory and the level of NO as well as the expressions of nNOS-LI or α₇nAChR-LI were obviously decreased in MLA+L-Arg+CC group or in L-NAME+L-Arg+CC group. In conclusion, i.c.v. administration of L-Arg combined with CC significantly improved the action of the L-Arg or CC on the content of NO and the nNOS or α₇nAChR expressions in hippocampus along with the learning and memory behavior of rats; when nNOS or α₇nAChR was interrupted in advance, the effects of L-Arg combined with CC were also suppressed. The results suggest that there are probably synergistic effects between NO and nAChR on learning and memory.

Key words: Nitric oxide; α7 nicotinic acetylcholine receptor; L-arginine; choline chloride; synergetic effect; Y-maze; learning and memory

收稿日期：2013-11-10　　录用日期：2014-03-07

通讯作者：祁文秀　　E-mail: fycqwx@163.com

引用本文：

荆治华, 未小明, 王少虎, 陈宇飞, 刘丽霞, 祁文秀. 一氧化氮和烟碱型乙酰胆碱受体在大鼠学习记忆中的联合作用[J]. 生理学报 2014; 66 (3): 307-314.

JING Zhi-Hua, WEI Xiao-Ming, WANG Shao-Hu, CHEN Yu-Fen, LIU Li-Xia, QI Wen-Xiu. [The synergetic effects of nitric oxide and nicotinic acetylcholine receptor on learning and memory of rats.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (3): 307-314 (in Chinese with English abstract).