远志总皂苷对AD模型大鼠海马nAChRα4及PSD-95表达的影响

神经药理学报 ›› 2011, Vol. 1 ›› Issue (3): 16-22.

远志总皂苷对AD模型大鼠海马nAChRα4及PSD-95表达的影响

李晓峰¹，赵大鹏¹，陈树沙¹，景玮²，李新毅²

1.山西医科大学第一临床医学院，神经内科， 030001，太原
2.山西医学科学院，神经内科，030031，太原

出版日期:2011-06-26 发布日期:2012-06-28
通讯作者: 李新毅，男，主任医师，神经病学/神经生理学博士，博士生导师；研究方向：老年性痴呆和脑血管病
作者简介:李晓峰，男，山西医科大学在读硕士；研究方向：老年性痴呆、脑血管病；Email：xiaofengli_2011@163.com
基金资助:
国家自然科学基金项目（No.801173455）

The Effects of Tenuigenin on Expression of nAChRα4 and PSD95 in Alzheimer’s Disease Model Rats

Li Xiao-feng¹，Zhao Da-peng¹，Chen Shu-sha¹，Jing Wei²，Li Xin-yi²

1. Department of Neurology，The First Clinical Medical School，Shanxi Medical University，Taiyuan Shanxi, 030001，China 2. Shanxi Academy of Medical Science，Taiyuan, 030031，China

Online:2011-06-26 Published:2012-06-28

摘要/Abstract

摘要： 目的:通过观察中药远志总皂苷（Tenuigenin，TEN）对阿尔茨海默病(Alzheimer’s disease，AD)模型大鼠烟碱型乙酰胆碱受体α4亚基（Nicotinic Acetylcholine Receptor subunit alpha-4，nAChRα4）和突触后致密蛋白95 (postsynaptic density 95，PSD-95)表达的影响，旨在探讨TEN对AD干预作用的机制。方法：32只雄性Wistar大鼠随机分为对照组，模型组，TEN 12.5，37.5 mg·mL^-1剂量组，应用D-半乳糖致衰老的基础上定向Meynert基底核损毁建立AD大鼠模型，TEN12.5，37.5 mg·mL^-1治疗组则在造模的同时用远志总皂苷灌胃(ig)治疗，采用免疫组化方法来检测大鼠海马CA1区nAChRα4及PSD-95的表达。结果: 模型组大鼠海马CA1区nAChRα4及PSD-95平均灰度值显著高于对照组，平均光密度值显著降低(P<0.01)；TEN 12.5，37.5 mg·mL^-1剂量组大鼠海马nAChRα4及PSD-95平均灰度值显著低于模型组，两组平均光密度值均显著增高(P<0.05)；且TEN 37.5 mg·mL^-1剂量组的平均灰度值比TEN 12.5 mg·mL^-1剂量组显著降低，平均光密度值显著增高(P<0.01)。结论：TEN可显著提高AD模型大鼠海马CA1区nAChRα4及PSD-95的表达，并具有剂量依赖性，这可能是其改善认知功能的部分机制。

关键词: 远志总皂苷, 阿尔茨海默病, 海马, nAChR&, alpha, 4, PSD-95

Abstract: Objective： To investigate the effects and the underlying mechanisms of Tenuigenin on Alzheimer’s disease by observing the effects of Tenuigenin(TEN) on expression of nicotinic acetylcholine receptor subunit alpha-4 (nAChRα4) and postsynaptic density 95(PSD-95) in Alzheimer’s disease model rat. Methods： 32 male Wistar rats were divided randomly into four groups: control group，model group，12.5 mg·mL^-1dose TEN group and 37.5 mg·mL^-1 dose TEN group. The rat model with Alzheimer’s disease was made by injecting ibotenic acid into Meynert basal nuclei of aging rat induced by D-gal.The expressions of nAChRα4 and PSD-95 in the hippocampus CA1 were measured by immunohistochemistry method. Results： Compared with the control group，the average gray-scale values of hippocampus CA1 nAChRα4 and PSD-95 in the model group were increased significantly and the average optical density was decreased obviously (P<0.01). Compared with the model group，the average gray-scale values in the hippocampus CA1 of 37.5 mg·mL^-1 dose TEN group and 12.5 mg·mL^-1 dose TEN group were obviously decreased and the average optical density was increased significantly (P<0.05). Meanwhile，the average gray-scale value within the hippocampus CA1 of 37.5 mg·mL^-1 dose TEN group was significantly less than that in 12.5 mg·mL^-1dose TEN group，but more distinct than that on the average optical density aspect (P<0.01). Conclusion： TEN can dose-dependently increase the expression of CA1 area nAChRα4 and PSD-95 in Alzheimer’s disease model rats，which may partly explain the beneficial effects of TEN on cognitive function.

Key words: Tenuigenin, Alzheimer&, rsquo, s disease, hippocampus, nAChR&, alpha, 4, PSD-95

中图分类号:

R961

李晓峰, 赵大鹏, 陈树沙, 景玮, 李新毅. 远志总皂苷对AD模型大鼠海马nAChRα4及PSD-95表达的影响[J]. 神经药理学报, 2011, 1(3): 16-22.

Li Xiao-feng, Zhao Da-peng, Chen Shu-sha, Jing Wei, Li Xin-yi. The Effects of Tenuigenin on Expression of nAChRα4 and PSD95 in Alzheimer’s Disease Model Rats[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(3): 16-22.

参考文献

1  Yuki Takada-Takatori，Toshiai Kume，Yasuhiko Izumi，et al. Roles of nicotinic receptors in acetylcholinesterase inhibitor-induced neuroprotection and nicotinicreceptor up-regulation [J]. Biol Pharm Bull，2009，32(3):318-324
2   Guan Zhizhong，Zhang Xiao，Ravid Ravid，Nordberg Agneta. Decreased protein levels of nicotinic Receptor subunits in the hippocampus and temporal cortex of patients with Alzheimer’s disease [J]. J Neurochem，2000，74 (1):237-243
3 Mary B Kennedy . Signal-processing machines at the postsynaptic density [J]. Science.2000，290(5492):750-754
4   陈勤，高晨曦，葛礼浩，陈小峰.远志皂苷对脑定位注射Aβ1-40拟AD大鼠脑内神经形态病理学变化的影响[J].激光生物学报，2006，15(3):294-298
5   谢宁，柳琳，周妍妍，何秀丽，邹纯朴.地黄饮子对老年性痴呆模型大鼠脑组织NO、NOS含量及行为学的影响[J].中国中医药科技，2004，3(11):84-85
6  郭宇飞，李新毅，郭芬，曹杜娟.中药远志对D-半乳糖致衰大鼠学习记忆及海LTP的影响[J].中国老年学杂志，2011，31(4):632-634
7   关彩宣，孙妠，曲鹏，张朝东. 鹅膏蕈氨酸对大鼠海马神经元的毒性作用[J].中国公共卫生，2006，22(9):1115-1116
8   Steven D.Buckingham ，Andrew K.Jones ，Laurence A.Brown ，David B.Sattelle . Nicotinic acetylcholine receptor signaling: roles in Alzheimer’s disease and amyloid neuroprotection [J]. Pharmacol Rev，2009，61(1):39-61
9  Antoine Taly，Pierre-Jean Corringer ，Denis Guedin，Pierre Lestage，Jean-Pierre Changeux . Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system [J]. Nat Rev Drug Discov.2009，8(9):733-750
10 Outi Salminen，Karen L.Murphy，J.Michael McIntosh，et al. Subunit composition and pharmacology of two classes of striatal presynaptic nicotinic acetylcholine receptors mediating dopamine release in mice [J]. Mol Pharmacol 2004，65(6):1526-1535
11 Ana Pocivavsek，Laura Icenogle，Edward D Levin. Ventral hippocampal alpha7 and alpha4beta2 nicotinic receptor blockade and clozapine effects on memory in female rats [J]. Psychopharmacology (Berl).2006，188(4):597-604
12 Paul D.Coleman，Pamela J.Yao. Synaptic slaughter in Alzheimer’s disease [J]. Neurobiol Aging，2003，24(8):1023-1027
13 侯筱宇，张光毅. NMDA受体信号复合体中蛋白质的相互作用[J].生命科学，2003，15(5):274-278
14 Martine Migaud ，Paul Chatlesworth，Maureen Dempster，et al. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein [J].Nature，1998，396(6710):433-439
15 吴伯智，谢珣，赵冬芹，蔡昭林，杨美燕，李楚华.远志皂苷对小鼠行为习得及海马CA3区突触形态的影响[J].华南师范大学学报，2011，2(1):111-115
16 陈庆林，陈勤，金蓓蓓.远志皂苷对AD小鼠学习记忆能力及中枢胆碱能系统标志酶活性的影响[J].中药药理与临床，2011，27(3):33-36

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