摘要
目的探讨慢性应激对大鼠胃功能和胃肠神经系统的影响,并分析其海马谷氨酸(Glu)离子型受体机制。方法通过建造慢性应激性抑郁模型大鼠,结合脑立体定位及微量注射Glu和N-甲基-D-天冬氨酸(NMDA)受体阻断剂MK-801,对实验鼠进行糖水偏爱等行为学检测、胃内压记录及胃内在神经丛的一氧化氮合酶(NOS)阳性神经元表达的组织化学检测。结果慢性不可预见性温和应激(CUMS)动物表现出抑郁样行为,且胃运动减弱;海马注射NMDA受体阻断剂MK-801,可以反转CUMS的效应;海马注射Glu,能增加游泳不动时间,但对胃运动无影响。CUMS使胃肌间神经丛NOS阳性神经元数量减少[(73.74±16.38)/LPF,P<0.05],神经节数量减少[(4.25±1.34)/LPF,P<0.05],但每个神经节内神经元数量明显增加(6.55±2.37,P<0.05);海马注射MK-801能改善CUMS引起的神经节数量减少的现象。结论慢性应激诱发的抑郁样行为与海马Glu及其NMDA受体有关,而胃活动的减弱可能与海马NMDA受体变化影响胃肌间神经丛NOS神经元分布格局有关。
Objective To investigate the involvement of hippocampal glutamate and NMDA receptor in the effect of CUMS on gastric function and enteric nervous system (ENS). Methods Chronic unpredictability mild stress (CUMS)-induced depression model was established in SD rats, intra-hippocampal mieroinjections of Glu and non- competitive antagonist of N-methyl-D-aspartie acid (NMDA) receptor ( MK-801 ) were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by sucrose preference test and forced swimming test. The intra-gastric pressure was recorded and the expression of Nitric oxide synthase (NOS) positive neurons in myenteric nerve plexus in stomach was detected as well. Results CUMS rats showed depression-like behavioral changes and weaker gastric motility as compared to control. Pretreated with MK-801 could reverse these CUMS effect, while microinjection of Glu, instead of CUMS, could increase the duration of immobility in forced swimming test, but has no effect on gastric motility. CUMS rats had lower expression of NOS positive neurons[ (73.74± 16. 38)/LPF, P 〈 0. 05 ] and positive ganglions number [ (4. 25 ±1.34 )/LPF, P 〈 0. 05 ] compared with control, but the number of NOS positive neurons in every ganglion was increased (6. 55 ±2. 37, P 〈 O. 05 ). Pretreated with MK-801 may rescue the decline of the number of positive ganglions. Conclusion CUMS may regu- late the activity of NMDA receptor in hippocampus, change the configuration of NOS positive neurons in ENS and weaken the gastric motility. While the effects of CUMS on depression-like behavioral changes due to both Glu and NMDA receptor in hippocampus.
出处
《基础医学与临床》
CSCD
北大核心
2012年第2期195-200,共6页
Basic and Clinical Medicine
基金
陕西师范大学国家级大学生创新性实验计划(091071804)
关键词
CUMS
海马
谷氨酸
胃运动
NOS
chronic unpredictability mild stress(CUMS)
hippocampus
Glu
gastric motility
NOS