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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 effect of tetrahydroxy stilbene glucoside (TSG) on brain hippocampal lesion in gerbils with cerebral ischemia / reperfusion (I / R) and its possible mechanism. Methods The whole brain I / R model of gerbil was established by ischemia of bilateral carotid arteries in gerbils for 30 min and reperfusion for 5 days. The gerbils were randomly divided into 6 groups: sham operation group, model control group, TSG large, medium and small dose groups (6, 3 and 1.5 mg / kg) and positive control group edaravone injection group (3 mg / kg) . After 5 days, Morris water maze was used to measure the learning and memory function of gerbil; Nissl staining was used to observe the changes of neuronal structure and number of hippocampal CA1 region in gerbil; TUNEL staining was used to observe neuronal apoptosis in hippocampal CA1 region of gerbil; Western blot Method to detect the expression of active-caspase-3 in brain tissue. Results Compared with the sham-operation group, the learning and memory abilities of gerbils in I / R group were significantly decreased. The neurons in hippocampal CA1 area were largely lost and the structure was disturbed. At the same time, the number of apoptotic neurons in hippocampus CA1 of I / R group increased significantly, while caspase-3 in brain tissue was significantly activated. TSG medium and high doses (3, 6 mg / kg) and Edaravone positive control group can significantly improve I / R-induced decline in learning and memory in gerbils, inhibit neuronal loss in the hippocampal CA1 area and improve the nerve Yuan structure; inhibit the apoptosis of CA1 neurons and caspase-3 activation. The TSG low-dose group of these changes have no significant therapeutic effect. Conclusion TSG has a significant therapeutic effect on I / R-induced brain injury, especially delayed neuronal apoptosis in the hippocampus, which is related to the inhibition of caspase-3 activation.