Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats

LI Yongge; ZHOU Shu; LIU Qingchun; WEI Xiaoming; ZHANG Dong; MA Fengqiao

doi:10.6039/j.issn.1001-0408.2023.19.09

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Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats

更新时间：2025-09-26

- Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats
- ZHONGGUO YAOFANG Vol. 34, Issue 19, Pages: 2350-2355(2023)
- 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：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.19.09
  CLC： R965
- Received：30 March 2023，
  
  Revised：2023-08-13，
  
  Accepted：14 August 2023，
  
  Published：15 October 2023
- 稿件说明：
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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[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[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 shor

tened 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

Keywords

references

SCHMIDT D ， LÖSCHER W . Drug resistance in epilepsy：putative neurobiologic and clinical mechanisms [J ] . Epilepsia ， 2005 ， 46 （ 6 ）： 858 - 877 .

ABRAHAMS S ， MORRIS R G ， POLKEY C E ， et al . Hippocampal involvement in spatial and working memory：a structural MRI analysis of patients with unilateral mesial temporal lobe sclerosis [J ] . Brain Cogn ， 1999 ， 41 （ 1 ）： 39 - 65 .

张菲菲 . 癫痫发作与炎症反应的关系及对大鼠认知功能的影响 [D ] . 兰州：兰州大学， 2017 .

ZHANG F F . The relationship between epileptic seizures and inflammatory reaction and its influence on cognitive function in rats [D ] . Lanzhou ： Lanzhou University ， 2017 .

杨峰彪，张祎年 . 小胶质细胞在癫痫中作用的研究进展 [J ] . 中国临床神经外科杂志， 2021 ， 26 （ 9 ）： 729 - 731 .

YANG F B ， ZHANG Y N . Research progress on the role of microglia in epilepsy [J ] . Chin J Clin Neurosurg ， 2021 ， 26 （ 9 ）： 729 - 731 .

KALKMAN H O ， FEUERBACH D . Modulatory effects of α7nAChRs on the immune system and its relevance for CNS disorders [J ] . Cell Mol Life Sci ， 2016 ， 73 （ 13 ）： 2511 - 2530 .

蒋永莹，李霖，沈卫星，等 . 乙酰胆碱通过作用于α7烟碱型乙酰胆碱受体抑制大鼠小胶质细胞炎性反应 [J ] . 生理学报， 2018 ， 70 （ 1 ）： 33 - 39 .

JIANG Y Y ， LI L ， SHEN W X ， et al . Acetylcholine suppresses microglial inflammatory response in rats via ac- ting on microglial α7nAChR [J ] . Acta Physiol Sin ， 2018 ， 70 （ 1 ）： 33 - 39 .

HAN Z Y ， SHEN F X ， HE Y ， et al . Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress [J ] . PLoS One ， 2014 ， 9 （ 8 ）： e105711 .

WANG X L ， DENG Y X ， GAO Y M ， et al . Activation of α7nAChR by PNU-282987 improves synaptic and cognitive functions through restoring the expression of synaptic-associated proteins and the CaM-CaMKⅡ-CREB signa- ling pathway [J ] . Aging ， 2020 ， 12 （ 1 ）： 543 - 570 .

薛萍 . α7烟碱乙酰胆碱能受体通过JAK2/STAT3通路激活脑内抗炎性小胶质细胞对脓毒症脑病大鼠的脑保护作用及机制研究 [D ] . 青岛：青岛大学， 2021 .

XUE P . Effect of α7 nicotinic acetylcholinergic receptor on polarization anti-inflammatory microglia via JAK2/STAT3 pathway in septic encephalopathy rats and its mechanism [D ] . Qingdao ： Qingdao University ， 2021 .

AMARAL C L D ， MARTINS Í C A ， VERAS A C C ， et al . Activation of the α7 nicotinic acetylcholine receptor prevents against microglial-induced inflammation and insulin resistance in hypothalamic neuronal cells [J ] . Cells ， 2022 ， 11 （ 14 ）： 2195 .

王芳，侯自立，韩冰，等 . 桑椹花青素-3-葡萄糖苷对癫痫模型小鼠的保护作用及海马BDNF/TrkB通路的影响 [J ] . 中国药房， 2020 ， 31 （ 3 ）： 335 - 339 .

WANG F ， HOU Z L ， HAN B ， et al . Study on protection effect of mulberry anthocyanin-3 glucoside on epilepsy model mice and the effect of hippocampal BDNF/TrkB path way [J ] . China Pharm ， 2020 ， 31 （ 3 ）： 335 - 339 .

OLBRICH A ， URAK L ， GRÖPPEL G ， et al . Semiology of temporal lobe epilepsy in children and adolescents in latera- lizing the seizure onset zone [J ] . Epilepsy Res ， 2002 ，48 （ 1 / 2 ）： 103 - 110 .

朱丹 . 癫痫的诊断与治疗：临床实践与思考 [M ] . 北京：人民卫生出版社， 2017 ： 120 .

ZHU D . Diagnosis and treatment of epilepsy [M ] . Beijing ： People’s Medical Publishing House ， 2017 ： 120 .

YANKAM N J ， COSTES N ， BOUILLOT C ， et al . Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using[ 11 C ] -（R）-PK11195 PET and MRI [J ] . J Cereb Blood Flow Metab ， 2017 ， 37 （ 4 ）： 1251 - 1263 .

THERAJARAN P ， HAMILTON J A ， O’BRIEN T J ， et al . Microglial polarization in posttraumatic epilepsy：potential mechanism and treatment opportunity [J ] . Epilepsia ， 2020 ， 61 （ 2 ）： 203 - 215 .

BOER K ， SPLIET W G ， VAN RIJEN P C ， et al . Evidence of activated microglia in focal cortical dysplasia [J ] . J Neuroimmunol ， 2006 ， 173 （ 1/2 ）： 188 - 195 .

TANG Y ， LE W D . Differential roles of M1 and M2 microglia in neurodegenerative diseases [J ] . Mol Neurobiol ， 2016 ， 53 （ 2 ）： 1181 - 1194 .

LIU J ， LI C Y ， PENG H W ， et al . Electroacupuncture attenuates learning and memory impairment via activation of α7nAChR-mediated anti-inflammatory activity in focal cerebral ischemia/reperfusion injured rats [J ] . Exp Ther Med ， 2017 ， 14 （ 2 ）： 939 - 946 .

ZHAO Q P ， YIN C Y ， YUAN Y ， et al . Down-regulation of miR-145 improves learning and memory abilities in epileptic rats by regulating hippocampal neuron apoptosis [J ] . World Neurosurg ， 2019 ， 122 ： e1432 - e1438 .

LEE I ， YOGANARASIMHA D ， RAO G ， et al . Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3 [J ] . Nature ， 2004 ， 430 （ 6998 ）： 456 - 459 .

BARAM T Z ， DONATO F ， HOLMES G L . Construction and disruption of spatial memory networks during deve- lopment [J ] . Learn Mem ， 2019 ， 26 （ 7 ）： 206 - 218 .

MÁTYÁS A ， BORBÉLY E ， MIHÁLY A . Hippocampal sclerosis in pilocarpine epilepsy：survival of peptide-containing neurons and learning and memory disturbances in the adult NMRI strain mouse [J ] . Int J Mol Sci ， 2021 ， 23 （ 1 ）： 204 .

AHMED Z ， SHAW G ， SHARMA V P ， et al . Actin-binding proteins coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry [J ] . J Histochem Cytochem ， 2007 ， 55 （ 7 ）： 687 - 700 .

LAWRENCE T . The nuclear factor NF-κB pathway in inflammation [J ] . Cold Spring Harb Perspect Biol ， 2009 ， 1 （ 6 ）： a001651 .

LEI W ， DUAN Z J . Advances in the treatment of cholinergic anti-inflammatory pathways in gastrointestinal disea- ses by electrical stimulation of vagus nerve [J ] . Digestion ， 2021 ， 102 （ 2 ）： 128 - 138 .

ZHENG L M ， SHI L ， ZHOU Z Y ， et al . Placental expression of AChE，α7nAChR and NF-κB in patients with preeclampsia [J ] . Ginekol Pol ， 2018 ， 89 （ 5 ）： 249 - 255 .

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