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大鼠脑创伤后一氧化氮合酶对学习和记忆功能的影响
引用本文:宋朝彦,崔建忠,洪军,王春生. 大鼠脑创伤后一氧化氮合酶对学习和记忆功能的影响[J]. 蚌埠医学院学报, 2009, 34(7): 558-562
作者姓名:宋朝彦  崔建忠  洪军  王春生
作者单位:1. 河北省保定市第一医院神经外科, 071000;2. 河北省唐山工人医院神经外科, 063000
摘    要:目的:探讨神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)和诱生型一氧化氮合酶(inducible nitric oxide synthase,iNOS)对大鼠创伤性颅脑损伤(traumatic brain injury,TBI)后空间学习和记忆的影响及7-硝基吲哚(7-nitroindazole,7-NI)和氨基胍(aminoguanidine,AG)的治疗作用。方法:将250只Wistar大鼠随机分成5组,按照Marmarou方法造成大鼠重型弥漫性TBI,免疫组化检测海马CA1区nNOS和iNOS表达情况,原位细胞DNA断裂检测(TUNEL)法检测海马CA1区凋亡细胞,采用Morris水迷宫测试各组大鼠的空间学习和记忆情况。结果:大鼠TBI后海马CA1区存在nNOS和iNOS明显表达,nNOS在伤后6h左右达高峰(P<0.05),iNOS在伤后3天左右达高峰(P<0.05)。TUNEL阳性细胞于伤后3天达高峰(P<0.05),伤后6h7-NI治疗组和联合治疗组与创伤组比较减少明显(P<0.05),伤后3天各治疗组均减少,且以联合治疗组减少最为明显(P<0.05)。结论:大鼠TBI后学习和记忆功能下降与NOS过表达引起的神经毒性作用有关。7-NI和AG通过抑制nNOS和iNOS的活性或表达起到神经保护作用,改善了大鼠的学习和记忆功能。

关 键 词:脑损伤   一氧化氮合酶   细胞凋亡   学习障碍   记忆障碍   大鼠
收稿时间:2009-04-10

Study on the effect of nitric oxide synthase on the learning and memorizing ability of rats after traumatic brain injury
SONG Chao-yan,CUI Jian-zhong,HONG Jun,WANG Chun-sheng. Study on the effect of nitric oxide synthase on the learning and memorizing ability of rats after traumatic brain injury[J]. Journal of Bengbu Medical College, 2009, 34(7): 558-562
Authors:SONG Chao-yan  CUI Jian-zhong  HONG Jun  WANG Chun-sheng
Affiliation:1. Department of Neurosurgery, The First Hospital of Baoding, Baoding Hebei 071000;2. Department of Neurosurgery, Gongren Hospital of Tangshan, Tangshan Hebei 063000, China
Abstract:Objective:To explore the influence of neuronal nitric oxide synthase(nNOS)and inducible nitric oxide synthase(iNOS)on the spatial learning ability and memory of rats following traumatic brain injury(TBI),and to observe the curative effect of 7-nitroindazole(7-NI)and aminoguanidine(AG).Methods:Two hundred and fifty male Wistar rats were randomly divided into 5 groups.Severe closed brain injury models were made according to Marmarou;immunohistochemical staining was used to detect the expression of nNOS and iNOS in the hippocampus CA1 region of the rats;TUNEL in situ was applied in determination of the apoptosis cells in the hippocampus CA1 region;the spatical learning ability and memory of the rats after injury was measured by means of Morris Water maze.Results:nNOS and iNOS expressed significantly in the hippocampus CA1 region of the rats.nNOS immuno-reactivity peaked at 6hr after injury(P<0.05),iNOS peaked at 3 days after injury(P<0.05),and TUNEL positive cells peaked at 3 days after injury(P<0.05).The number of positive cells decreased significantly 6 hours after injury in the treatment groups compared with that in the trauma group(P<0.05).And 3 days after injury,positive cells decreased in all the three groups,with the combination therapy group the most obvious.Conclusions:The decrease of learning and memorizing ability of the rats after TBI is associated with the nerve toxicity of NOS.7-NI and AG protect the nerve by inhibiting the activity and expression of nNOS and iNOS,which may improve the spatial learning ability and memory of rats.
Keywords:brain injuries  nitric oxide synthase  learning disorders  memory disorders  rats
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