甲基苯丙胺暴露对神经病理性蛋白APP及p-tau表达的影响

发布时间：2018-08-26 18:15

【摘要】：目的 :观察甲基苯丙胺(methamphetamine,Meth)暴露后神经病理性蛋白β-淀粉样前体蛋白(amyloid precursor protein,APP)及p-tau表达的改变。方法 :将30只C57BL/6J雄性小鼠随机分为对照组、生理盐水组,Meth组,Meth组腹腔注射给予10 mg/kg的剂量,1 d 2次,连续7 d。利用高尔基银染法观察Meth作用后大脑神经元数量及棘突的改变;采用Western blot法检测Meth暴露后神经病理性蛋白APP,p-tau表达的改变。结果:高尔基银染结果显示,Meth组与生理盐水组及对照组比较,神经元数量及棘突显著减少。通过Western blot发现Meth能剂量依赖及时间依赖性上调病理性蛋白β-APP及p-tau的表达,具有显著性差异(P0.05)。此外,通过预孵L型钙通道的抑制剂硝苯地平,发现Meth引起的APP及p-tau上调显著被抑制。结论:Meth暴露可引起阿尔兹海默样病变,因而该研究可为Meth引起认知能力下降提供部分解释。
[Abstract]:Aim: to observe the expression of 尾 -amyloid precursor protein (amyloid precursor protein,APP) and p-tau after exposure to methamphetamine (methamphetamine,Meth). Methods: thirty male C57BL/6J mice were randomly divided into two groups: the control group (n = 30) and the control group (n = 30). The rats in the control group were given intraperitoneal injection of 10 mg/kg for 1 d for 7 days. The changes of the number of neurons and spinous process in the brain after Meth were observed by Golgi silver staining, and the expression of neuropathic protein APP,p-tau after Meth exposure was detected by Western blot method. Results: the results of Golgi silver staining showed that the number of neurons and spinous process in Meth group were significantly lower than those in normal saline group and control group. Western blot showed that Meth could up-regulate the expression of 尾 -APP and p-tau in dose-dependent and time-dependent manner (P0.05). In addition, the up-regulation of APP and p-tau induced by Meth was significantly inhibited by nifedipine, an inhibitor of L-type calcium channel. ConclusionMeth exposure may cause Alzheimer like lesions, so this study may provide a partial explanation for cognitive impairment induced by Meth.
【作者单位】：南京医科大学公共卫生学院;南京医科大学第一附属医院急诊医学中心;
【基金】：国家自然科学基金(81202230,81673213) 江苏省自然科学基金(BK20151557) 江苏省科技厅重点病种规范化诊疗研究(BL2014088)
【分类号】：R749.64

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