二苯乙烯苷对沙鼠脑缺血/再灌注引发海马损伤的保护作用

中国临床解剖学杂志 ›› 2013, Vol. 31 ›› Issue (2): 180-183.

二苯乙烯苷对沙鼠脑缺血/再灌注引发海马损伤的保护作用

王齐^1,2，　陈晓宇¹，　刘梅梅^1,3，　王栋¹，　孙玉花¹，　陈晓蓉¹

1.安徽医科大学组胚教研室，合肥 230032；　 2.安徽医学高等专科学校生物化学教研室，合肥 230601；
3. 安徽医学高等专科学校组胚教研室，合肥 230601

收稿日期:2012-10-17 发布日期:2013-04-08
通讯作者: 陈晓宇,副教授，硕士生导师，E-mail:cxyayd@ yahoo.com.　cn E-mail:41722315@qq.com
作者简介:王齐（1978-），男，讲师,安徽省合肥市人,在读硕士,主要从事神经退行性疾病机制的研究,Tel:13956937250
基金资助:
安徽省教育厅自然科学研究项目（KJ2010A183）；安徽省自然科学资金（1208085MC53）；安徽医科七年制 “早期接触科研”训练计划项目（2011-ZQKY-06）

Protection and mechanism of tetrahydroxy stilbene glucoside on hippocampal ischemia-reperfusion injury in gerbils

WANG Qi ^1,2，CHEN Xiao-yu¹, LIU Mei-mei ^1,3, WANG Dong¹, CHEN Xiao-rong¹, SUN Yu-hua¹

1.Department of Histology and Embryology, Anhui Medical University, Hefei 230032,China; 2.Department of Biochemistry, Anhui Medical College, Hefei 230061；3.Department of Histology and Embryology, Anhui Medical College, Hefei 230601, China

Received:2012-10-17 Published:2013-04-08

摘要/Abstract

摘要：

目的　研究二苯乙烯苷（tetrahydroxy stilbene glucoside, TSG）对脑缺血/再灌注（ischemia/reperfusion, I/R）沙鼠脑海马损伤的保护作用及可能机制。方法采用结扎沙鼠双侧颈动脉缺血30 min，再灌注5 d复制沙鼠全脑I/R模型。沙鼠随机分为6组，假手术组、模型对照组、TSG大、中、小剂量（6、3、1.5 mg/kg）组和阳性对照药依达拉奉注射组（3 mg/kg）。5 d后通过Morris水迷宫测定沙鼠学习记忆功能；Nissl染色观察沙鼠大脑海马CA1区神经元结构和数量的变化；TUNEL染色法观察沙鼠大脑海马CA1区神经元凋亡的变化；Western blot法检测脑组织active-caspase-3的表达。结果　与假手术组相比，I/R组沙鼠学习记忆能力明显降低，海马CA1区神经元大量丢失，结构紊乱。同时，I/R组沙鼠CA1区神经元凋亡数量明显增加，脑组织中caspase-3显著活化。TSG中、高（3、6 mg/kg）剂量组和依达拉奉阳性对照组均可以显著改善I/R引发的沙鼠学习记忆能力的降低，抑制海马CA1区神经元的丢失，改善神经元结构；抑制CA1区神经元的凋亡以及caspase-3的活化。而TSG低剂量组对上述变化均没有明显的治疗作用。结论　TSG对于I/R引发的脑损伤，尤其是海马区神经元迟发性凋亡具有明显的治疗作用，这种作用与其抑制caspase-3的活化相关。

关键词: 缺血再灌注, 二苯乙烯苷, 海马神经元, 凋亡

Abstract:

Objective　To investigate the protective effects of tetrahydroxy stilbene glucoside (TSG) on ischemia-reperfusion (I/R)-induced hippocampal injury and the underlying mechanisms in gerbils.　Methods Gerbil global I/R model was established by clamping bilateral carotid arteries for 30 min followed by reperfusion for 5 days. Animals were divided into 6 groups randomly: Sham, I/R, I/R+TSG high, middle, low (6, 3, 1.5 mg/kg) and edaravone injection group (3 mg/kg). The functions of learning and memory were detected by Morris water maze 5 days after reperfusion. The number and structure of neurons and neuronal apoptosis in hippocampal CA1 region were evaluated by Nissl and TUNEL staining, respectively. In addition, the expression of active-caspase-3 in cerebral tissues was measured by Western blot.　Results　Compared to Sham group, learning and memory capacity of gerbils in I/R group declined significantly, the number of functional neurons in hippocampal CA1 region decreased dramatically. Furthermore, the apoptotic neurons indicated by TUNEL staining as well as caspase-3 activation increased remarkably. TSG administration at middle and high dose (3, 6 mg/kg) and edaravone injection significantly reversed aforementioned changes induced by I/R. In contrast, TSG administration at low dose (1.5 mg/kg) had no effect.　Conclusion　TSG had therapeutic effects on I/R induced cerebral injury, especially on delayed neuron apoptosis in hippocampal CA1 region, which may be related to its suppression effect on caspase-3 activation.

Key words: Ischemia-reperfusion, Tetrahydroxy stilbene glucoside, Hippocampal neuron, Apoptosis

中图分类号:

王齐, 陈晓宇, 刘梅梅, 王栋, 孙玉花, 陈晓蓉. 二苯乙烯苷对沙鼠脑缺血/再灌注引发海马损伤的保护作用[J]. 中国临床解剖学杂志, 2013, 31(2): 180-183.

WANG Ji, CHEN Xiao-Yu, LIU Mei-Mei, WANG Dong, SUN Yu-Hua, CHEN Xiao-Rong. Protection and mechanism of tetrahydroxy stilbene glucoside on hippocampal ischemia-reperfusion injury in gerbils[J]. Chinese Journal Of Clinical Anatomy, 2013, 31(2): 180-183.

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