解剖学报

解剖学报 ›› 2023, Vol. 54 ›› Issue (3): 283-288.doi: 10.16098/j.issn.0529-1356.2023.03.005

• 神经生物学 • 上一篇    下一篇

普兰林肽对5×FAD小鼠和WT小鼠认知行为及脑和视网膜β淀粉样蛋白6E10、炎症因子和神经细胞形态的影响

侯翌葳1 杨宇1 王博2 段英涛1 姚宏波3*
  

  1. 1. 齐齐哈尔医学院基础医学院2018级，黑龙江 齐齐哈尔 161006; 2. 逊克县人民医院普外科，黑龙江 黑河 164499; 3. 齐齐哈尔医学院基础医学院组织学胚胎学教研室，黑龙江 齐齐哈尔 161006
  • 收稿日期:2022-06-01 修回日期:2022-08-27 出版日期:2023-06-06 发布日期:2023-06-06
  • 通讯作者: 姚宏波 E-mail:22868204@qq.com
  • 基金资助:
    黑龙江省教育厅基本科研业务费基础研究项目

Effects of pranlinide on cognitive behavior, β amyloid protein 6E10, inflammatory factors and neuronal cell morphology in brain and retina of 5×FAD mice and WT mice

HOU  Yi-wei1 YANG  Yu1  WANG  Bo2  DUAN  Ying-tao1  YAO  Hong-bo3*   

  1. 1. Grade 2018, Basic Medical Science College, Qiqihar Medical University, Heilongjiang Qiqihaer161006, China;2. Department of General Surgery, Xunke County People’s Hospital, Heilongjiang Heihe164499, China;3. Department of Histology and Embryology, Basic Medical Science College, Qiqihar Medical University, Heilongjiang Qiqihar161006, China
  • Received:2022-06-01 Revised:2022-08-27 Online:2023-06-06 Published:2023-06-06
  • Contact: YAO Hong-bo E-mail:22868204@qq.com
  • Supported by:
    Basic research project of basic scientific research business expenses of Heilongjiang Provincial Department of Education

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摘要：

目的 探讨普兰林肽对5×FAD小鼠和WT小鼠认知行为及脑和视网膜的β淀粉样蛋白（Aβ）6E10、炎症因子和神经细胞形态的影响。  方法 实验选取5×FAD小鼠32只、WT小鼠16只，均为雌性。随机将5×FAD小鼠分为空白组、治疗组；WT组不进行任何处理；空白组腹腔注射PBS溶液；治疗组每天腹腔注射1次普兰林肽［200 μg/(μ·d)］， 治疗8周。Morris水迷宫实验测定其认知行为的变化；采用免疫组织化学检测小鼠海马组织细胞、视网膜中Aβ6E10蛋白的表达；ELISA测定肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）炎症因子的含量。HE染色测定小鼠海马组织中神经细胞的排列和形态。  结果 治疗组的潜伏时间短于5×FAD组，差异有统计学意义（P<0.05）；治疗组的穿越平台次数和目标象限停留百分比高于5×FAD组，差异有统计学意义（P<0.05）；5×FAD组脑内和视网膜内的Aβ6E10面积高于治疗组，差异具有统计学意义（P＜0.05）；视网膜和脑内的Aβ6E10具有正相关（P＜0.05）。治疗组与5×FAD组脑中和视网膜中的TNF-α和IL-1β比较，差异无统计学意义（P>0.05）。治疗组较5×FAD组神经细胞排列规则，边界清晰。  结论 普兰林肽可以改善小鼠的认知能力；使神经细胞排列较为规整，形态规则边界清晰；神经胶质细胞分布集中；周围间隙减小；脑内和视网膜内Aβ6E10具有同步性。

关键词: 普兰林肽, 阿尔茨海默病, β淀粉样蛋白6E10, 肿瘤坏死因子α, 白细胞介素1β, 酶联免疫吸附测定, 小鼠

Abstract:

Objective To study the effects of pranlinide on cognitive behavior, β amyloid(Aβ) protein 6E10, inflammatory factors and neuronal cell morphology in brain and retina of 5×FAD mice and WT mice.   Methods Thirty two 5×FAD mice and 16 WT mice were selected. All were female 5×FAD mice were randomly divided into blank group and treatment group; No treatment was given in WT group. Blank group was intraperitoneally injected with PBS; treatment group was received intraperitoneal injection of pranlinide once a day for 8 weeks. The changes of cognitive ability were measured by Morris water maze test. The expression of Aβ6E10 protein in mice hippocampal cells and retina was detected by immunohistochemistry. Tumor necrosis factor-α(TNF-α) was determined by enzyme-linked immunosorbent assay. The same method  was also used for interleukin-1β(IL-1β) detection (the content of inflammatory factors). The arrangement and morphology of nerve cells in mouse hippocampal tissue were determined by hematoxylin-eosin (HE) staining.   Results  The latency time of treatment group was shorter than that of 5×FAD group，and the times of crossing the platform and the percentage of target quadrant stay in the treatment group were higher than those in the 5×FAD group, and the differences were statistically significant (P<0.05). Compared with the retinal area and the brain area of Aβ6E10 in the 5×FAD group and in the treatment group, the content was halved (P<0.05). There was positive correlation between Aβ6E10 in retina and brain (P<0.05).There was no significant difference in TNF-α and IL-1β in brain and retina between treatment group and 5×FAD group (P>0.05). Compared with the 5×FAD group, the nerve cells in the treatment group were arramged in order and clear relatively. The distribution of glial cells was concentrated; The surrounding clearance was small.   Conclusion Pranlinide can improve the cognitive ability of mice. The arrangement of nerve cells is regular, the shape is regular and the boundary is clear; The distribution of glial cells is concentrated; Surrounding of clearance decrease. Aβ6E10 is synchronized in brain and retina.

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