PNU-282987对颞叶癫痫模型大鼠认知功能的影响及机制

李永格; 周舒; 刘庆春; 未小明; 张冬; 马凤巧

doi:10.6039/j.issn.1001-0408.2023.19.09

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PNU-282987对颞叶癫痫模型大鼠认知功能的影响及机制

药学研究 | 更新时间：2023-10-09

- PNU-282987对颞叶癫痫模型大鼠认知功能的影响及机制
- Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats
- 中国药房 2023年34卷第19期页码：2350-2355
- 作者机构：
  
  1.南阳医学高等专科学校基础医学部，河南南阳　473000
  2.昆明医科大学生物医学工程研究中心，昆明　650000
- 作者简介：
  
  副教授，硕士。研究方向：癫痫发生机制与治疗。 E-mail：liyongge19810719@aliyun.com
- 基金信息：
  
  河南省科技发展计划项目(212102310837);河南省高等学校青年骨干教师培养计划项目(2018GGJS253);南阳市科技计划项目(JCQY026)
- DOI：10.6039/j.issn.1001-0408.2023.19.09
  中图分类号： R965
- 纸质出版日期：2023-10-15，
  
  收稿日期：2023-03-30，
  
  修回日期：2023-08-13，
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李永格,周舒,刘庆春等.PNU-282987对颞叶癫痫模型大鼠认知功能的影响及机制 ^Δ[J].中国药房,2023,34(19):2350-2355.

LI Yongge,ZHOU Shu,LIU Qingchun,et al.Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats[J].ZHONGGUO YAOFANG,2023,34(19):2350-2355.
李永格,周舒,刘庆春等.PNU-282987对颞叶癫痫模型大鼠认知功能的影响及机制 ^Δ[J].中国药房,2023,34(19):2350-2355. DOI： 10.6039/j.issn.1001-0408.2023.19.09.

LI Yongge,ZHOU Shu,LIU Qingchun,et al.Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats[J].ZHONGGUO YAOFANG,2023,34(19):2350-2355. DOI： 10.6039/j.issn.1001-0408.2023.19.09.

摘要

目的

研究特异性α7烟碱型乙酰胆碱受体（α7nAChR）激动剂PNU-282987对颞叶癫痫（TLE）模型大鼠认知功能的影响及机制。

方法

将60只大鼠随机分为对照组、模型组、PNU-282987组（3 mg/kg）和甲基牛扁亭（MLA）+PNU-282987组（6 mg/kg MLA+3 mg/kg PNU-282987），每组15只。除对照组之外，其余各组大鼠均制备TLE模型。造模成功后，各组大鼠腹腔注射相应药物或生理盐水，每天1次，连续2周。观察大鼠癫痫发作行为并进行评分，记录发作持续时间；检测大鼠认知功能；观察海马组织CA1区神经元病理学形态；检测海马组织中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和IL-1β水平；检测海马组织中离子钙接头蛋白1（IBA-1）阳性表达和α7nAChR、核因子κB（NF-κB）p65、磷酸化NF-κB p65（p-NF-κB p65）蛋白表达水平。

结果

与模型组比较，PNU-282987组大鼠癫痫评分和发作持续时间，海马组织中IBA-1阳性细胞数量和TNF-α、IL-6、IL-1β水平以及NF-κB p65、p-NF-κB p65蛋白表达水平均显著减少/降低（

＜0.05）；逃避潜伏期时间显著缩短（

＜0.05），原平台象限停留时间及穿越平台次数均显著增加（

＜0.05）；海马组织CA1区神经元损伤明显减轻；海马组织中α7nAChR蛋白表达水平显著升高（

＜0.05）。与PNU-282987组比较，MLA+PNU-282987组大鼠上述指标均显著逆转（

＜0.05）。

结论

PNU-282987可改善TLE模型大鼠的认知功能障碍，其机制可能是通过激活α7nAChR/NF-κB信号通路，抑制小胶质细胞介导的炎症反应，进而减轻海马神经元损伤。

Abstract

OBJECTIVE

To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats.

METHODS

Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected.

RESULTS

Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF-α， IL-6 and IL-1β， the expressions of NF-κB p65 and p-NF-κB p65 protein decreased significantly in the hippocampus （

＜0.05）； the escape latency time was shortened significantly （

＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （

＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （

＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （

＜0.05）.

CONCLUSIONS

PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF-κB signaling pathway， thus reducing hippocampal neuronal damage.

关键词

PNU-282987癫痫α7nAChR/NF-κB信号通路小胶质细胞炎症反应

Keywords

epilepsyα7nAChR/NF-κB signaling pathwaymicrogliainflammatory response

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