海马干细胞来源的外泌体对血管性痴呆大鼠学习记忆能力改善作用及其机制探究
Effect of exosomes derived from hippocampal stem cells on learning and memory in rats with vascular dementia and its mechanism
潘成利 1黄月萍 1薛炬君 1陈曦 1齐丹 1侯晓君 1孙爽 1王喜春 1付宏娟1
作者信息
- 1. 黑龙江省医院老年神经内科,黑龙江哈尔滨 150036
- 折叠
摘要
目的 分析海马干细胞来源的外泌体对血管性痴呆大鼠学习记忆能力改善作用及其机制.方法 取新生SD大鼠海马组织,提取海马干细胞外泌体.成年特殊清洁级(SPF)健康雄性SD大鼠90只,随机分为假手术组、模型组及外泌体组,每组30只,检测各组大鼠学习记忆能力、氧化应激因子水平、海马组织病理学变化、海马组织因子、脑微血管密度以及凋亡相关因子变化.结果 透射显微镜观察到海马干细胞来源外泌体结构呈圆形或椭圆形杯状结构的小囊泡,其结构完整,直径50～100 nm之间;特异性标记蛋白CD9、CD63表达阳性.与假手术组比较,模型组大鼠逃避潜伏期及错误次数明显延长,平台区域探索时间及有效区停留时间明显缩短,MDA、AchE、ET-1、VEGF、Bax水平均明显升高,SOD、5-HT、Bcl-2水平均明显降低,脑微血管内皮细胞明显减少(P＜0.05);与模型组对比,外泌体组大鼠逃避潜伏期明显缩短,平台区域探索时间及有效区停留时间明显延长,MDA、AchE、ET-1、VEGF、Bax水平均明显降低,SOD、5-HT、Bcl-2水平均明显升高,脑微血管内皮细胞明显增多(P＜0.05).假手术组大鼠海马组织细胞排列紧密,结构清晰,大小、形态一致,且具有丰富的尼氏小体;模型组大鼠海马组织细胞排列紊乱,形态、结构不完整,尼氏小体数量明显减少;外泌体组大鼠海马组织较模型组明显改善,细胞形态较模型组明显完整,尼氏小体数量增多.结论 海马干细胞来源的外泌体能够明显改善血管性痴呆大鼠的学习记忆能力,对海马神经元损伤起到一定的保护作用,其作用机制可能与抑制氧化应激与细胞凋亡,调控神经递质含量,促进脑微血管密度有关.
Abstract
Objective To analyze the effect and mechanism of exosomes derived from hippocampal stem cells on learning and memory ability in vascular dementia rats.Methods Hippocampal stem cell exosomes were extracted from newborn SD rats,and observed and recorded by transmission microscope.90 male SD rats were divided into the sham operation group,the model group and the exosome group randomly,with 30 rats in each group.The vascular dementia model of rats was established.The learning and memory ability,oxidative stress factor level,hippocampal histopatholog-ical changes,hippocampal tissue factor,brain microvessel density and apoptosis related factors were detected.Results Small vesicles with round or oval cup-shaped structure were observed by transmission microscope,and their structures were complete,with a diameter of 50～100 nm.The positive expression of specific marker proteins CD9 and CD63 was detected by protein imprinting.Compared with the sham operation group,the escape latency and the number of errors in the model group were significantly prolonged,the exploration time in the platform area and the residence time in the ef-fective area were significantly shortened,the levels of MDA,ache,ET-1,VEGF and Bax were significantly increased,the levels of SOD,5-HT and Bcl-2 were significantly decreased,and the cerebral microvascular endothelial cells were signif-icantly reduced(P＜0.05);Compared with the model group,the escape latency of rats in the exosome group was signifi-cantly shortened,the exploration time in the platform area and the residence time in the effective area were significantly prolonged,the levels of MDA,ache,ET-1,VEGF and Bax were significantly decreased,the levels of SOD,5-HT and Bcl-2 were significantly increased,and the cerebral microvascular endothelial cells were significantly increased(P＜0.05).The hippocampal cells of sham operated rats were closely arranged,with clear structure,consistent size and shape,and abundant Nissl bodies;In the model group,the arrangement of hippocampal cells was disordered,the mor-phology and structure were incomplete,and the number of Nissl bodies decreased significantly;Compared with the mod-el group,the hippocampal tissue of the exosome group was significantly improved,the cell morphology was significantly complete,and the number of Nissl bodies increased.Conclusion Exosomes derived from hippocampal stem cells can significantly improve the learning and memory ability of vascular dementia rats and protect hippocampal neuron dam-age.Its mechanism may be related to inhibiting oxidative stress and apoptosis,regulating neurotransmitter content and promoting brain microvessel density.
关键词
海马干细胞/外泌体/血管性痴呆/学习记忆能力/作用机制Key words
hippocampal stem cells/exosomes/vascular dementia/learning and memory ability/action mechanism引用本文复制引用
基金项目
黑龙江省科技厅联合引导项目(LH2021H064)
出版年
2024
NETL
NSTL
万方数据