Lin Yiqin, Kang Zhenming, Su Changsheng, Li Shunyuan, Xie Wenqin
Department of Anesthesiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, China.
Mol Ther Methods Clin Dev. 2024 Feb 5;32(1):101207. doi: 10.1016/j.omtm.2024.101207. eCollection 2024 Mar 14.
The aim of this research was to explore the therapeutic capabilities of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) that had been subjected to heat shock pretreatment, in treating psychiatric disorders induced by sleep deprivation in mice. The EVs were isolated and characterized, while western blotting was utilized to assess the expression of exosomal markers and heat shock protein 70 (HSP70). To evaluate the impact of EV treatment on anxiety-like behavior and cognitive impairment in sleep-deprived (SD) mice, the open field test, plus maze test, and Y-maze task were conducted. Heat shock pretreatment significantly increased the expression of HSP70 in EVs. Administration of EVs from heat shock-pretreated hUC-MSCs improved anxiety-like behavior and cognitive function in SD mice. Furthermore, EV treatment promoted synaptic protein expression, HSP70 expression and inhibited neuroinflammation in the hippocampus of SD mice. Western blotting analysis also revealed that EV treatment reduced the levels of TLR4 and p65 in the hippocampus. EVs from heat shock-pretreated hUC-MSCs have therapeutic potential for sleep deprivation-induced psychiatric disorders by regulating neuroinflammation and synaptic function in mice.
本研究的目的是探索经热休克预处理的人脐带间充质干细胞（hUC-MSCs）衍生的细胞外囊泡（EVs）在治疗小鼠睡眠剥夺诱导的精神疾病方面的治疗能力。对EVs进行了分离和表征，同时利用蛋白质免疫印迹法评估外泌体标志物和热休克蛋白70（HSP70）的表达。为了评估EV治疗对睡眠剥夺（SD）小鼠焦虑样行为和认知障碍的影响，进行了旷场试验、高架十字迷宫试验和Y迷宫任务。热休克预处理显著增加了EVs中HSP70的表达。给予经热休克预处理的hUC-MSCs来源的EVs可改善SD小鼠的焦虑样行为和认知功能。此外，EV治疗促进了SD小鼠海马体中突触蛋白表达、HSP70表达，并抑制了神经炎症。蛋白质免疫印迹分析还显示，EV治疗降低了海马体中TLR4和p65的水平。经热休克预处理的hUC-MSCs来源的EVs通过调节小鼠的神经炎症和突触功能，对睡眠剥夺诱导的精神疾病具有治疗潜力。
