摘要
目的:研究白藜芦醇(resveratrol,Res)预处理对脑缺血再灌注(ischemia reperfusion,I/R)大鼠海马区Wnt/β-catenin信号通路相关蛋白的表达量、星形胶质细胞及神经元形态的影响,探讨白藜芦醇对脑缺血再灌注大鼠海马区神经元损伤的保护作用机制。方法:将SD大鼠60只随机分为四组,每组15只:正常对照组(Control)、假手术组(Sham)、缺血再灌注组(I/R)和白藜芦醇治疗组(Res)。Res组大鼠连续7 d腹腔注射白藜芦醇(每日30 mg/kg,由2%DMSO溶解),Sham组和I/R组注射同等量2%DMSO;7 d后Res组和I/R组采用改良线栓法制备大鼠大脑中动脉阻塞(middle cerebral artery occlusion,MACO)模型,缺血90 min,再灌注24 h。Sham组仅分离暴露一侧颈内动脉,不插入线栓;24 h后对各组大鼠进行神经功能学评分;脑组织TTC染色;尼氏染色;免疫组化检测海马区GSK-3β和星型胶质细胞(GFAP)数量及形态变化;Western Blot分别检测Wnt信号通路相关因子GSK-3β、p-GSK-3β、β-catenin蛋白水平表达量。结果:再灌注24 h后,尼氏染色显示与I/R组相比Res组海马区仅有少量的神经元破碎和消失,形态尚完整(P<0.05),同时行为学评分和梗死面积也低于I/R组(P<0.05)。免疫组化显示,与I/R组相比Res组GSK-3β的表达量明显降低,伴随星形胶质细胞活化状态和数量减少(P<0.05)。Western Blot显示,与免疫组化表达趋势结果一致Res组GSK-3β的的表达量明显低于I/R组,而p-GSK-3β、β-catenin的表达量均增高(P<0.05)。结论:白藜芦醇可能是通过调节Wnt/β-catenin信号通路相关蛋白的表达进而有效的降低大鼠脑缺血再灌注后神经元的损伤。
Objective： To investigate the mechanism and effect of resveratrol （RES） on ischemia/reperfusion （I/R） induced hippocampus damage in the brain of rat. Methods ： SD rats were randomly divided into four groups （ 15 rats for each group） ： Control group （Control）, Sham operation group （Sham）, ischemia reperfusion group （I/R） and resvera- trol treatment group （Res）. The rats in Res group were given intraperitoneal injection of resveratrol （30 mg/kg for days, dissolved by 2% DMSO solution） for 7 consecutive days, Control group, Sham group and I/R group were injected with the same amount of 2% DMSO ; 7 days later, Res group and I/R group were used to establish a rat model of middle cerebral artery occlusion （MACO） with 90 min ischemia followed by 24 reperfusion. Sham group was only exposed to one side of the internal carotid artery without fishing line. After 24 hours, the rats were evaluated by neurological score; Nissl stai-ning; TrC staining of brain tissue; the number and morphological changes of GSK-3β and astrocytes （GFAP） in hippo- campus were detected by lmmunohistochemical. Wnt signaling related factor GSK-3β, p-GSK-3β, beta-catenin protein expression level were detected by Western Blot. Results： After reperfusion for 24 hours, Nissl staining showed that Res group only a small number of neurons in the hippocampus of were broken and disappeared compared with the I/R group, the morphology was still intact （ P 〈 0.05 ） ; The Res group behavior score and infarct size were also lower than I/R group （ P 〈 0.05）. Immunohistochemistry showed that the Res group expression of GSK-3β was significantly Decreases com- pared with I/R group, at the same time accompanied by the activation status and decrease number of astrocytes （P 〈 0.05）. Western Blot results consistent with the trend of immunohistochemically expression. The expression of GSK-3β in the Res group was lower than I/R group, while the p-GSK-3β and beta-catenin was higher than I/R group （P 〈0.05）. Conclusion： Resveratrol protects the hippocampus neurons against cerebral ischemic reperfusion-induced damage may be via regulating the Wnt/beta-catenin signaling pathway in rats.
出处
《神经解剖学杂志》
CSCD
北大核心
2017年第5期611-616,共6页
Chinese Journal of Neuroanatomy
