脑内糖原磷酸化酶抑制剂对大鼠急性癫痫发作神经炎症及记忆减退的改善作用*

doi:10.12047/j.cjap.6283.2022.076

中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (5): 406-411.doi: 10.12047/j.cjap.6283.2022.076

脑内糖原磷酸化酶抑制剂对大鼠急性癫痫发作神经炎症及记忆减退的改善作用^*

邓筱悦^1,2, 帅念念¹, 刘时彦¹, 侯立力², 田绍文^1,3Δ

1.桂林医学院基础医学院广西脑与认知神经科学重点实验室, 广西桂林 541199;
2.南华大学附属南华医院麻醉科, 湖南衡阳 421002;
3.南华大学衡阳医学院生理学教研室, 湖南衡阳 421001

收稿日期:2022-02-14 修回日期:2022-08-18 出版日期:2022-09-28 发布日期:2023-04-23
通讯作者: ^△Tel: 15240782684; E-mail: 47089887@qq.com
基金资助:
^*国家自然科学基金项目(32160197);广西自然科学基金项目(2020GXNSFAA159001)

Glycogen phosphorylase inhibitor ameliorates pentylenetetrazole-induced acute seizure, neuroinflammation and memory impairment in rats^*

DENG Xiao-yue^1,2, SHUAI Nian-nian¹, LIU Shi-yan¹, HOU Li-li², TIAN Shao-wen^1,3Δ

1. Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541199;
2. Department of Anesthesiology, Nanhua Affiliated Hospital, University of South China, Hengyang 421002;
3. Department of Physiology, Hengyang Medical College, University of South China, Hengyang 421001, China

Received:2022-02-14 Revised:2022-08-18 Online:2022-09-28 Published:2023-04-23

摘要/Abstract

摘要： 目的: 探讨脑内糖原磷酸化酶(GP)的抑制剂1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇(DAB)对戊四氮(PTZ)致痫模型大鼠急性发作、神经炎症及记忆减退的改善作用。方法: 实验一,将大鼠随机分为2组即Vehicle组(n=5)与PTZ组(n=5),腹腔注射生理盐水或PTZ(70 mg/kg)后30 min,取海马组织,Western blot检测GP表达水平,比色法检测乳酸水平。实验二,将大鼠随机分为4组即Vehicle+Vehicle组(n=18)、DAB+Vehicle组(n=18)、Vehicle+PTZ组(n=19)与DAB+PTZ组(n=18)。侧脑室注射PBS或DAB(50 μg/2 μl)后15 min,腹腔注射生理盐水或PTZ(70 mg/kg)。行为学与Racine评分评价急性发作程度,Western blot检测海马组织目标蛋白水平,新物体识别记忆测试评价记忆能力。 结果: ① 与Vehicle组比较,PTZ组海马组织GP表达水平与乳酸水平均显著升高(P＜0.01)。② 与Vehicle+PTZ组比较,DAB+PTZ组肌阵挛潜伏期、前肢阵挛潜伏期、全身阵挛潜伏期均显著升高(P＜0.01),而全身阵挛持续时间、癫痫发作程度则显著降低(P＜0.01)。③ 与Vehicle+Vehicle组比较,Vehicle+PTZ组海马组织IL-1β、IL-6、TNF-α、IBA-1、GFAP表达水平均显著上升(P＜0.01),而新物体识别测试中辨别指数则显著降低(P＜0.01);与Vehicle+PTZ组比较,DAB+PTZ组海马组织IL-1β、TNF-α、IBA-1、GFAP表达水平均显著降低(P＜0.01),而辨别指数则显著升高(P＜0.01)。此外,各组大鼠对两物体总探究时间无显著性组间差异(P＞0.05);PTZ注射后48 h各组大鼠自发活动能力无显著性组间差异(P＞0.05)。结论: DAB改善PTZ诱导大鼠急性发作、神经炎症及记忆减退,提示DAB具有潜在的抗癫痫临床应用前景。

关键词: 癫痫, 星形胶质细胞, 糖原磷酸化酶, DAB, 乳酸, 大鼠

Abstract: Objective: In the present study, we determined whether the glycogen phosphorylase(GP)inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) ameliorates pentylenetetrazole (PTZ)-induced acute seizure, neuroinflammation and memory impairment in rats. Methods: In experiment 1, rats were randomly divided into the Vehicle (n=5) and PTZ (n=5) groups, and received intraperitoneal injection of saline or PTZ (70 mg/kg), respectively. Hippocampal tissues were collected 30 min after drug injection. Western blot was used to examine the levels of GP expression. Colorimetric assay was used to determine the levels of lactate. In experiment 2, rats were randomly divided into the Vehicle+Vehicle (n=18), DAB+Vehicle (n=18), Vehicle+PTZ (n=19) and DAB+PTZ (n=18) groups. Rats received intracerebroventricular injection of PBS or DAB (50 μg/2 μl) 15 min before receiving intraperitoneal injection of saline or PTZ (70 mg/kg). Behavioural assays and the Racine scale were used to evaluate seizure severity. Western blot was used to examine the levels of targeted protein of hippocampal tissues. Novel object recognition test was used to assess memory performance. Results: ① Compared with the Vehicle group, the levels of GP and lactate in the hippocampal tissues of the PTZ group were increased significantly (both P＜0.01). ② Compared with the Vehicle+PTZ group, in the DAB+PTZ group, the levels of myoclonic body jerk latency, forelimb clonus latency and tonic-clonic seizure latency were increased significantly (all P＜0.01), while the duration of seizure and seizure scores were decreased significantly (both P＜0.01). ③ Compared with the Vehicle+Vehicle group, in the Vehicle +PTZ group, the levels of IL-1β, IL-6, TNF-α, IBA-1 and GFAP in the hippocampal tissues were increased significantly (all P＜0.01), and the discrimination index in the novel object recognition test was decreased significantly (P＜0.01). Compared with the Vehicle+PTZ group, in the DAB+PTZ group, the levels of IL-1β, TNF-α, IBA-1 and GFAP in the hippocampal tissues were decreased significantly (all, P＜0.01), while the discrimination index in the novel object recognition test was increased significantly (P＜0.01). Conclusion: DAB ameliorates PTZ-induced seizure, neuroinflammation and memory impairment in rats, suggesting that DAB may serve as a novel agent for potential clinical treatment of epilepsy.

Key words: epilepsy, astrocyte, glycogen phosphorylase, DAB, lactate, rat

中图分类号:

R742.1

邓筱悦, 帅念念, 刘时彦, 侯立力, 田绍文. 脑内糖原磷酸化酶抑制剂对大鼠急性癫痫发作神经炎症及记忆减退的改善作用^*[J]. 中国应用生理学杂志, 2022, 38(5): 406-411.

DENG Xiao-yue, SHUAI Nian-nian, LIU Shi-yan, HOU Li-li, TIAN Shao-wen. Glycogen phosphorylase inhibitor ameliorates pentylenetetrazole-induced acute seizure, neuroinflammation and memory impairment in rats^*[J]. CJAP, 2022, 38(5): 406-411.

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脑内糖原磷酸化酶抑制剂对大鼠急性癫痫发作神经炎症及记忆减退的改善作用^*

Glycogen phosphorylase inhibitor ameliorates pentylenetetrazole-induced acute seizure, neuroinflammation and memory impairment in rats^*

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脑内糖原磷酸化酶抑制剂对大鼠急性癫痫发作神经炎症及记忆减退的改善作用*

Glycogen phosphorylase inhibitor ameliorates pentylenetetrazole-induced acute seizure, neuroinflammation and memory impairment in rats*

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脑内糖原磷酸化酶抑制剂对大鼠急性癫痫发作神经炎症及记忆减退的改善作用^*

Glycogen phosphorylase inhibitor ameliorates pentylenetetrazole-induced acute seizure, neuroinflammation and memory impairment in rats^*