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右旋美托咪啶对惊厥性癫痫持续状态大鼠认知功能和神经炎症的影响 预览

Dexmedetomidine attenuats seizure and enhances cholinergic anti-inflammatory pathway in rats with convulsive status epilepticus
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摘要 目的惊厥性癫痫持续状态(CSE)是一种神经元异常放电引起的严重神经系统疾病,能导致海马损伤和认知障碍。该研究旨在探讨右旋美托咪啶(DEX)对CSE大鼠认知功能和神经炎症的影响。方法90只Sprague-Dawley大鼠均分为对照组、CSE组和DEX组。Morris水迷宫试验测量认知功能。进行急性海马切片以检测长时程增强(LTP)。免疫组织化学法检测海马α7烟碱乙酰胆碱受体(α7-nAChR)的表达。酶联免疫吸附试验(ELISA)测定海马组织白细胞介素-1β(IL-1β),肿瘤坏死因子-α(TNF-α),S-100β和脑源性神经营养因子(BDNF)水平。结果DEX明显改善CSE引起的认知功能障碍、降低癫痫发作严重程度、增加LTP的振幅和持续时间。DEX增加CSE大鼠海马组织α7-nAChR表达,降低海马IL-1β,TNF-α和S-100β水平,增加BDNF水平。α7-nAChR激动剂尼古丁可以模拟DEX对癫痫发作严重程度和LTP的改善作用,但DEX的作用可以被α-银环蛇毒素(α-BGT)减弱。结论DEX显著改善CSE大鼠的空间认知功能障碍,癫痫发作严重程度降低和LTP增加,与DEX激活胆碱能抗炎通路密切相关。 Objective Convulsive status epilepticus(CSE)is a neurological disease with contraction and extension of limbs,leading to damage of hippocampus and cognition.This study aimed to explore the effects of dexmedetomidine(DEX)on the cognitive function and neuroinflammation in CSE rats.Methods All rats were divided into control group,CSE group and DEX group.Morris water maze test was used to measure cognitive function.Acute hippocampal slices were made to detect lonG^-term potentiation(LTP).Immunohistochemistry was used to determine the expression ofα7-nicotinic acetylcholine receptor(α7-nAChR).Enzyme-linked immunosorbent assay(ELISA)was used to measure serum levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),S-100βand brain-derived neurotrophic factor(BDNF).Results DEX improved the memory damage caused by CSE.DEX reduced seizure severity and increased the amplitudes and sustainable time of LTP,and also inhibited the hippocampal expression ofα7-nAChR in CSE rats.DEX treatment decreased hippocampal IL-1β,TNF-αand S-100βlevels and increased BDNF levels.The effects of DEX on seizure severity and LTP could be simulated by nicotine or attenuated by concurrentα-bungarotoxin(α-BGT)treatment.Conclusion DEX significantly improved spatial cognitive dysfunction,reduced seizure severity and increased LTP in CSE rats.Improvements by DEX were closely related to enhancement of cholinergic anti-inflammatory pathway.
作者 韩耀国 张涛 叶明荣 陈刚 姚玉龙 许开亮 孙跃喜 雷鸣 HAN Yaoguo;ZHANG Tao;YE Mingrong;CHEN Gang;YAO Yulong;XU Kailiang;SUN Yuexi;LEI Ming(Department of Critical Care Medicine,Senventh People's Hospital of Shanghai University of TCM,Shanghai 200137,China)
出处 《安徽医药》 CAS 2019年第7期1310-1315,共6页 Anhui Medical and Pharmaceutical Journal
基金 上海市卫生和计划生育委员会中医特色诊疗技术提升项目(zyjx-2017021) 浦东新区卫生系统重点学科建设资助项目(PWZxk2017-15).
关键词 癫痫持续状态 右美托咪啶 α7-烟碱乙酰胆碱受体 白细胞介素-1Β 脑源性神经营养因子 Status epilepticus Dexmedetomidine α7-nicotinic acetylcholine receptor Interleukin-1 Brain-derived neurotrophic factor
作者简介 通信作者:雷鸣,男,副主任医师,硕士生导师,研究方向为神经系统疾病,E-mail:leiming6891@163.com.
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