大鼠脑创伤后一氧化氮合酶对学习和记忆功能的影响

    Study on the effect of nitric oxide synthase on the learning and memorizing ability of rats after traumatic brain injury

    • 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。

       

      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.

       

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