Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role i...Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.展开更多
目的探讨山奈酚(kaempferol,KAE)对慢性脑缺血大鼠的作用及其机制。方法采用双侧颈总动脉永久性结扎(bilateral common carotid arteries occlusion,2VO)建立大鼠慢性脑缺血动物模型;Morris水迷宫、抓握实验检测大鼠行为学;尼氏染色及H...目的探讨山奈酚(kaempferol,KAE)对慢性脑缺血大鼠的作用及其机制。方法采用双侧颈总动脉永久性结扎(bilateral common carotid arteries occlusion,2VO)建立大鼠慢性脑缺血动物模型;Morris水迷宫、抓握实验检测大鼠行为学;尼氏染色及HE染色观察脑组织病理改变;比色法检测MDA含量和SOD活性;Western blot检测脑组织DJ-1蛋白表达水平。结果与2-VO模型组比较,KAE明显改善慢性脑缺血诱导的学习记忆障碍和抓握能力损伤。此外,KAE明显减轻2VO大鼠脑组织病理损伤,增高脑组织中SOD活性,提高海马和皮层中抗氧化蛋白DJ-1的表达水平。结论KAE明显改善慢性脑缺血诱导的大鼠认知功能障碍、四肢平衡能力障碍及病理损伤,其机制可能与提高体内抗氧化系统有关。展开更多
基金supported by the National Natural Science Foundation of China,No.82101567Doctoral Start-up Foundation of Liaoning Province,No.2021-BS-111345 Talent Project of Shengjing Hospital of China Medical University,No.M0673(all to XYF)。
文摘Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.
