摘要
目的探究M2型小胶质细胞外泌体对异氟烷致发育期大鼠神经元毒性的改善作用及其机制。方法7日龄SD大鼠随机分为对照组(Control组)、异氟烷组(ISO组)、M2型小胶质细胞外泌体组(M2-Exos组)、M2型小胶质细胞外泌体+过表达对照组(M2-Exos+ov-NC组)和M2型小胶质细胞外泌体+过表达USP14组(M2-Exos+ov-USP14组),每组10只。Morris水迷宫评价大鼠学习和记忆能力;HE染色和尼氏染色观察大鼠海马神经元损伤;TUNEL染色检测大鼠海马神经元凋亡水平;Western blot检测大鼠海马组织中USP14/PI3K/AKT信号通路表达。结果M2型小胶质细胞外泌体治疗降低异氟烷暴露的发育期大鼠逃避潜伏期,并增加大鼠穿越平台次数和目的象限停留时间,改善海马神经元损伤并抑制神经元凋亡,降低大鼠海马中USP14表达并增加PI3K和AKT磷酸化;过表达USP14逆转了M2型小胶质细胞外泌体治疗对异氟烷暴露的发育期大鼠认知功能障碍和海马神经元损伤的改善作用,以及PI3K和AKT磷酸化水平的上调作用。结论M2型小胶质细胞外泌体通过下调USP14改善异氟烷暴露的发育期大鼠认知功能障碍和海马神经元损伤。
Objective To explore the ameliorative effect of M2 microglia exosomes on isoflurane-induced neuronal toxicity in developmental rats and its mechanism.Methods Seven day-old SD rats were randomly divided into control group(Control group),isoflurane group(ISO group),M2 microglia exosomes group(M2-Exos group),M2 microglia exosomes+over-expression control group(M2-Exos+ov-NC group)and M2 microglia exosomes+over-expression USP14 group(M2 Exos+ov-USP14 group).Morris water maze was used to evaluate the learning and memory ability of rats.HE staining and Nissl staining were used to observe the injury of hippocampus neurons in rats.TUNEL staining was used to detect the apoptosis level of hippocampal neurons in rats.Western blot was used to detect the expressions of USP14/PI3K/AKT signaling pathway in rat hippocampus.Results The treatment of M2 microglia exosomes decreased the escape latency of isoflurane-exposed developmental rats,increased the number of crossing platforms and the residence time in the target quadrant,improved the damage of hippocampal neurons and inhibited neuronal apoptosis,decreased the expression of USP14 and increased the phosphorylation of PI3K and AKT.Overexpression of USP14 reversed the effects of M2 microglia exosomes therapy on cognitive dysfunction and hippocampal neuron injury in developmental rats exposed to isoflurane,and the up-regulation of PI3K and AKT phosphorylation levels.Conclusion M2 microglia exosomes can improve cognitive dysfunction and hippocampal neuron damage in developmental rats exposed to isoflurane by down regulating USP14.
作者
张晓敏
范嘉宁
李松泽
杜薇
ZHANG Xiao-min;FAN Jia-ning;LI Song-ze;DU Wei(Department of Anesthesiology,Cancer Hospital of China Medical University,Liaoning Cancer Hospital and Institute,Shenyang 110042,China)
出处
《解剖科学进展》
2025年第5期655-659,共5页
Progress of Anatomical Sciences
基金
辽宁省自然科学基金(2023-BS-044)。
