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卵类胱抑素诱导APP/PS1转基因小鼠中阿尔茨海默病相关蛋白表达的变化。

Ovocystatin Induced Changes in Expression of Alzheimer's Disease Relevant Proteins in APP/PS1 Transgenic Mice.

作者信息

Stanczykiewicz Bartlomiej, Gburek Jakub, Rutkowska Maria, Lemieszewska Marta, Gołąb Krzysztof, Juszczyńska Katarzyna, Piotrowska Aleksandra, Trziszka Tadeusz, Dzięgiel Piotr, Podhorska-Okołów Marzenna, Zabłocka Agnieszka, Rymaszewska Joanna

机构信息

Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, 50-367 Wroclaw, Poland.

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, 50-556 Wroclaw, Poland.

出版信息

J Clin Med. 2022 Apr 23;11(9):2372. doi: 10.3390/jcm11092372.

Abstract

Background: Ovocystatin is marked by structural and biological similarities to human cystatin C, which plays an important role in the course of neurodegenerative diseases. Recently, it has been shown that ovocystatin might prevent aging-related cognitive impairment in rats and reduce memory decline in an APP/PS1 mice model. Thus, this study aimed to assess the effect of ovocystatin on histopathological changes in APP/PS1 mice. Materials and methods: Ovocystatin was administered intraperitoneally for four weeks (40 μg/mouse) to 35-weeks-old transgenic (AD, n = 14) and wild type (NCAR, n = 15) mice (stock B6C3-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax). A histopathological evaluation comprised antibodies directed against β-amyloid (1:400, SIG-39320-1000, Covance) and Tau (1:4000, AHB0042, Invitrogen). Three regions of the hippocampus— the dentate gyrus (DG) and the cornu ammonis (CA1 and CA3)—were analyzed by immunohistochemistry in each animal. All differences are expressed as percentage relative to the control group. Results: The main results showed that the percentage of immunoreactive area of β-amyloid, tau protein deposits in APP/PS1+ovCYS was decreased in DG, CA1, and CA3 regions compared with the APP/PS1 control, respectively (p < 0.05). Conclusions: Ovocystatin caused significant changes in the expression pattern of all investigated proteins in hippocampal tissues both in APP/PS1 and NCAR mice.

摘要

背景

卵类胱抑素在结构和生物学特性上与人类胱抑素C相似,后者在神经退行性疾病的病程中起重要作用。最近有研究表明,卵类胱抑素可能预防大鼠与衰老相关的认知障碍,并减轻APP/PS1小鼠模型中的记忆衰退。因此,本研究旨在评估卵类胱抑素对APP/PS1小鼠组织病理学变化的影响。

材料与方法

对35周龄的转基因(AD,n = 14)和野生型(NCAR,n = 15)小鼠(品系B6C3-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax)腹腔注射卵类胱抑素四周(40μg/小鼠)。组织病理学评估包括针对β-淀粉样蛋白(1:400,SIG-39320-1000,Covance)和Tau蛋白(1:4000,AHB0042,Invitrogen)的抗体。对每只动物的海马体三个区域——齿状回(DG)和海马角(CA1和CA3)——进行免疫组织化学分析。所有差异均表示为相对于对照组的百分比。

结果

主要结果显示,与APP/PS1对照组相比,APP/PS1+ovCYS组DG、CA1和CA3区域中β-淀粉样蛋白免疫反应面积百分比、tau蛋白沉积分别降低(p < 0.05)。

结论

卵类胱抑素使APP/PS1和NCAR小鼠海马组织中所有研究蛋白的表达模式发生显著变化。

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