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。
Objective To investigate the protective effects oftetrahydroxy stilbene glucoside (TSG) on ischemia-reperfusion (IdR)-induced hippocampal injury and the underlying mechanisms in gerbils. Methods Gerbil global FR 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 UR 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 lfR. In contrast, TSG administration at low dose (1.5 mg/kg) had no effect. Conclusion TSG had therapeutic effects on UR induced cerebral injury, especially on delayed neuron apoptosls in hippocampal CA1 region, which may be related to its suppression effect on caspase-3 activation.
出处
《中国临床解剖学杂志》
CSCD
北大核心
2013年第2期180-183,共4页
Chinese Journal of Clinical Anatomy
基金
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)
关键词
缺血再灌注
二苯乙烯苷
海马神经元
凋亡
Ischemia-reperfusion
Tetrahydroxy stilbene glucoside
Hippocampal neuron
Apoptosis