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β-淀粉样蛋白对大鼠海马细胞线粒体-内质网结构耦联的影响

Effects of Aβ25-35 on mitochondria-endoplasmic reticulum structure coupling in rat hippocampus

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【作者】 孔庆博张金婵任锐

【Author】 KONG Qing-bo;ZHANG Jin-chan;REN Rui;College of Public Health,Harbin Medical University;

【通讯作者】 任锐;

【机构】 哈尔滨医科大学公共卫生学院毒理学教研室

【摘要】 目的研究β-淀粉样蛋白(Aβ25~35)对大鼠海马线粒体-内质网结构耦联(MAM)的影响。方法将48只健康成年清洁级雄性SD大鼠按体重随机分为6组,分别为对照(不进行任何处理)组、假手术(开颅进针但不注射溶液)组、生理盐水组和2.5、5、7.5μg/μl Aβ25~35染毒组,每组8只。于海马CA1区一次性注射2μl染毒。于手术后14 d,应用ELISA法检测大鼠血清中Aβ25~35水平,分别用RT-PCR和Western blotting检测海马内线粒体融合蛋白1(MFN1)、MFN2 m RNA及蛋白的表达水平。结果与对照组相比,5、7.5μg/μl Aβ25~35染毒组大鼠血清中的Aβ25~35水平均增高,差异有统计学意义(P<0.05);且随着Aβ25~35染毒浓度的升高,大鼠血清中的Aβ25~35水平呈上升趋势。与对照组相比,各浓度Aβ25~35染毒组大鼠海马组织中MFN1、MFN2蛋白和mRNA的表达水平均增高,除7.5μg/μl组MFN1 m RNA外,差异均有统计学意义(P<0.05);且随着Aβ25~35染毒浓度的升高,大鼠海马组织中MFN1蛋白及MFN2蛋白和mRNA的表达水平均呈先上升后下降的趋势,而大鼠海马组织中MFN1 mRNA的表达水平呈下降趋势。结论 Aβ25~35可以增加大鼠血清中β-淀粉样蛋白的水平,同时Aβ25~35可破环大鼠海马组织线粒体-内质网结构耦联结构,造成其功能异常,从而发挥神经毒性作用。

【Abstract】 Objective To understand the effects of β-amyloid(Aβ25-35) on mitochondria-endoplasmic reticulum structure coupling( MAM) in rat hippocampus. Methods A total of 48 adult male SD rats were randomly divided into six groups by weight:control group(no treatment),sham operation group(craniotomy,needling but no injection),saline group and 2.5,5 and 7.5 μg/μl Aβ25-35 exposure group,eight in each group. At the 14 th day after operation,detection of Aβ25-35 in serum of rats by ELISA was performed. mRNA and protein expression levels of MFN1,MFN2 in hippocampus were detected by RT-PCR and Western blot.Results Compared with the control group,the levels of Aβ25-35 in serum of the 5,7.5 μg/μl Aβ25-35 groups significantly increased(P <0.05),with a dose dependent manner.Compared with the control group,the expression levels of MFN1,MFN2 protein and mRNA in hippocampus of rats in the Aβ25-35 exposure groups were increased(P<0.05),except for MFN1 m RNA in the 7.5 μg/μl group. With the increase of Aβ25-35 concentration,the expression levels of MFN1 protein and MFN2 protein and mRNA in hippocampus of rats increased first and then decreased,while the expression level of MFN1 m RNA in hippocampus of rats decreased. Conclusion Aβ25-35 can increase the content of β-amyloid in serum,and disrupt the mitochondrial-endoplasmic reticulum structure coupling(MAM) of rat hippocampus,causing its abnormal function and exerting neurotoxicity.

【基金】 哈尔滨市科技计划青年科技创新人才项目(2013RFQXJ069)
  • 【文献出处】 环境与健康杂志 ,Journal of Environment and Health , 编辑部邮箱 ,2018年10期
  • 【分类号】R749.16
  • 【下载频次】13
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