吡格列酮对小鼠脑缺血再灌注海马区神经元损伤的影响

doi:10.3969/j.issn.1006-7795.2023.04.022

首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (4): 645-651.doi: 10.3969/j.issn.1006-7795.2023.04.022

吡格列酮对小鼠脑缺血再灌注海马区神经元损伤的影响

王荣亮¹, 闫峰¹, 田悦¹, 黄语悠¹, 罗玉敏 ^1*#, 马舒贝^2*#

1. 首都医科大学宣武医院脑血管病研究室，北京 100053；2. 大连理工大学附属中心医院神经内科，辽宁大连 116033

收稿日期:2023-09-22 出版日期:2023-08-21 发布日期:2023-07-26
通讯作者: 罗玉敏, 马舒贝 E-mail:yumin111@ccmu.edu.cn, mshb1980@vip.163.com
基金资助:
国家自然科学基金面上项目（82171301）, 北京市自然科学基金面上项目（7222083）, 辽宁省自然科学基金指导项目（2019-ZD-0884）, 大连市医学科学研究计划项目（1911005）

Effects of Pioglitazone on neuronal damage in the mouse hippocampus after middle cerebral artery occlusion and reperfusion

Wang Rongliang¹, Yan Feng¹, Tian yue¹, Huang Yuyou¹, Luo Yumin^1*#, Ma Shubei^2*#

1.Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; 2. Department of Neurology, Central Hospital of Dalian University of Technology, Dalian 116033, Liaoning Province, China

Received:2023-09-22 Online:2023-08-21 Published:2023-07-26
Supported by:
This study was supported by National Natural Science Foundation of China (82171301), Natural Science Foundation of Beijing (7222083), the Natural Science Foundation of Liaoning Province (2019-ZD-0884), Dalian City Medicine and Science Research Project (1911005).

摘要/Abstract

摘要： 目的研究吡格列酮对小鼠脑缺血再灌注后海马区神经元的影响，并对其作用机制进行探讨。方法将36只青年雄性C57BL/6J小鼠按随机数字表法完全随机分为3组：假手术组、对照组及吡格列酮组（n=12）。采用大脑中动脉闭塞（middle cerebral artery occlusion, MCAO）的方式制备小鼠脑缺血再灌注损伤模型。小鼠脑缺血后再灌注即刻按照25 mg/kg体质量的剂量灌胃吡格列酮或等体积的0.9%（质量分数）氯化钠注射液，每天1次，持续7 d。分别在术后3、7 d采用神经功能缺损程度评分（Neurological Severity Scores, NSS）对小鼠神经功能进行评估。术后7 d处死小鼠，脑组织制作石蜡切片，通过尼氏（Nissl）染色检测脑梗死百分比及小鼠脑组织皮质区、纹状体区、海马区的齿状回（dentate gyrus，DG）、CA1和CA3区的神经元数量；通过免疫印迹法检测脑组织海马区凋亡相关蛋白B-细胞淋巴瘤因子2（B-cell leukemia/lymphoma 2, Bcl2）和Bcl2关联X蛋白（Bcl2 associated X protein, Bax）的表达。结果与对照组小鼠比较，吡格列酮组小鼠在脑缺血后第3、7 d 的NSS评分差异无统计学意义，而脑梗死体积百分比则显著减小（P<0.05），皮质区和海马CA3区尼氏小体的数量显著升高（P<0.05），并伴随Bcl2/Bax比值的升高（P<0.05）。结论吡格列酮可以减轻小鼠脑缺血再灌注损伤后脑组织海马CA3区神经元丢失程度，其作用机制可能与调节海马区Bcl2/Bax比值有关。

关键词: 吡格列酮, 脑缺血, 神经元损伤, 神经保护

Abstract: Objective To investigate the potential neuroprotective effects and the underlying mechanisms of Pioglitazone(PGZ) on neuronal damage in mice after cerebral ischemia. Methods A total of 36 young-aged (2-month) C57 BL/6J mice were randomly divided into 3 group (n=12): sham group, vehicle group, and PGZ group. Mice were treated with PGZ (25 mg/kg) or saline for 7 d by intragastric administration after transient middle cerebral artery occlusion (MCAO). Neurological function was evaluated by Neurological Severity Sores (NSS) at 3, and 7 d after MCAO.Infarction volume and the number of neurons in cortex, striatum, and the hippocampal CA1, CA3, dentate gyms (DG) regions were measured by Nissl staining.Western blotting was used to assess the expression of apoptosis associated protein B-cell leukemia/lymphoma 2 (Bcl2) and Bcl2 associated X protein(Bax) at 7 d after MCAO. Results Compared to the vehicle-treated mice, PGZ-treated mice didn't exhibit better performance at 3, 7 d after MCAO surgery (P>0.05). However, PGZ reduced infarct volume of the brains, and PGZ also significantly ameliorated neuron loss in cortex and hippocampal CA3 region after cerebral injury compared with the vehicle group (P<0.05). Moreover, PGZ promoted the ratio of Bcl2 and Bax (P<0.05).Conclusions These results suggest that PGZ treatment alleviated the neuronal damage in hippocampal CA3region of mice with cerebral ischemia-reperfusion injury, which may be explained by PGZ regulated the ratio of Bcl2 and Baxin hippocampus.

Key words: Pioglitazone, cerebral ischemia, neuronal damage, neuroprotection

中图分类号:

王荣亮, 闫峰, 田悦, 黄语悠, 罗玉敏, 马舒贝. 吡格列酮对小鼠脑缺血再灌注海马区神经元损伤的影响[J]. 首都医科大学学报, 2023, 44(4): 645-651.

Wang Rongliang, Yan Feng, Tian yue, Huang Yuyou, Luo Yumin, Ma Shubei. Effects of Pioglitazone on neuronal damage in the mouse hippocampus after middle cerebral artery occlusion and reperfusion[J]. Journal of Capital Medical University, 2023, 44(4): 645-651.

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吡格列酮对小鼠脑缺血再灌注海马区神经元损伤的影响

Effects of Pioglitazone on neuronal damage in the mouse hippocampus after middle cerebral artery occlusion and reperfusion

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