亚硝基化的二硫键异构酶介导甲基苯丙胺致小鼠相关脑区α-突触核蛋白表达升高

发布时间：2018-01-15 06:03

  本文关键词：亚硝基化的二硫键异构酶介导甲基苯丙胺致小鼠相关脑区α-突触核蛋白表达升高　出处：《南方医科大学学报》2017年10期 　论文类型：期刊论文

  更多相关文章： 甲基苯丙胺 二硫键异构酶 亚硝基化 α-突触核蛋白 一氧化氮合酶

【摘要】：目的研究亚硝基化的二硫键异构酶(PDI)对甲基苯丙胺(METH)致小鼠海马及纹状体区α-突触核蛋白(α-SN)表达的影响。方法利用C57小鼠METH亚急性中毒模型,使用一氧化氮合酶(NOS)抑制剂N-硝基-L-精氨酸(L-NNA)与METH共同造模,实验分为对照组、L-NNA组、METH组、METH+L-NNA组。Western Blotting技术检测各组海马及纹状体区内一氧化氮合酶(NOS)、PDI及其S亚硝基化(PDI-SNO)和α-SN表达情况。一氧化氮试剂盒检测各组一氧化氮含量。结果 METH给药后NOS、一氧化氮含量、PDI-SNO、α-SN表达较对照组均明显升高(P0.05);L-NNA与METH共处理后与METH组对比,NOS表达下降(P0.05),一氧化氮含量明显减少(P0.05),能够显著抑制PDI-SNO表达(P0.05),伴随α-SN表达降低(P0.05)。而MET H+L-NNA组、L-NNA组与对照组比较均无明显差异(P0.05)。结论 METH作用后诱导NOS活化,一氧化氮含量升高,PDI发生显著S亚硝基化而功能失活,导致相关脑区α-SN表达升高,而NOS抑制剂L-NNA能部分缓解METH神经毒性作用。
[Abstract]:Objective to study the effect of nitrosated disulfide isomerase (PDI) on 伪 -synaptophysin (伪 -SN) in the hippocampus and striatum of mice induced by methamphetamine (METHs). Methods the subacute poisoning model of METH in C57 mice was used. Nnitro-L-arginine L-NNA), a nitric oxide synthase (NOS) inhibitor, was used to establish the model with METH. The model was divided into control group and L-NNA group. METH L-NNA group. Western Blotting technique was used to detect nitric oxide synthase (NOS) in hippocampus and striatum. The expression of PDI, PDI-SNOand 伪 -SN and the content of nitric oxide in each group were detected by nitric oxide kit. Results the contents of NOS and no were detected after METH administration. Compared with the control group, the expression of PDI-SNO and 伪 -SN increased significantly (P 0.05). Compared with METH group, L-NNA and METH decreased the expression of NOS and the content of nitric oxide (P0.05). It could significantly inhibit the expression of PDI-SNO and decrease the expression of 伪 -SN. However, the expression of 伪 -SN was decreased in MET H L-NNA group. There was no significant difference between L-NNA group and control group (P 0.05). Conclusion METH can induce the activation of NOS and increase the content of nitric oxide. In PDI, S-nitrosation and functional inactivation resulted in increased 伪 -SN expression in related brain regions, while L-NNA, an inhibitor of NOS, partially alleviated the neurotoxicity of METH.
【作者单位】： 南方医科大学法医学院;上海交通大学医学院附属新华医院;顺德职业技术学院医药卫生学院;广州市刑事科学技术研究所//广东省法医遗传学重点实验室;
【基金】：国家自然科学基金(81373240) 广东省自然科学基金(2014A030313300,2014A030310025)~~
【分类号】：R749.64
【正文快照】： 甲基苯丙胺(METH)属于苯丙胺类神经兴奋剂,在 世界范围内被广泛滥用,是当前对公共卫生和社会危害最大的毒品之一[1-2]。研究表明METH主要作用于中枢神经系统,结构与儿茶酚胺类神经递质相似,主要表现为多巴胺等单胺类神经末梢的损伤,可出现与帕金森病等神经退行性疾病相似的病，

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