神经干细胞分泌组通过调节小胶质细胞表型抑制体内外神经炎症

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摘要 目的： 探究神经干细胞分泌组(neural stem cell secretome，NSC-S)对体内外神经炎症的影响及作用机制。方法: 采用脂多糖诱导神经炎症小鼠模型，通过旷场实验评估NSC-S对小鼠行为学的影响，免疫荧光染色和尼氏染色评估NSC-S对脑皮质小胶质细胞表型和神经元损伤的影响；体外用脂多糖刺激诱导BV2小胶质细胞炎症模型，通过流式细胞术检测NSC-S对BV2细胞表型的影响，采用过氧化物酶体增殖物激活受体-γ(peroxisome proliferator activated receptor-γ,PPAR-γ)抑制剂GW9662研究NSC-S的抗炎机制。结果: 经NSC-S治疗的小鼠在旷场实验中运动总距离及平均运动速度均显著提高(P<0.05)，NSC-S调节小鼠脑皮质中小胶质细胞表型极化并抑制神经元损伤；NSC-S在体外抑制BV2细胞M1表面标志CD86表达(P<0.05)，促进M2表面标志CD206表达(P<0.01)，然而，GW9662阻断了NSC-S对BV2细胞表型的调节作用(P<0.05)。结论: NSC-S通过调节小胶质细胞表型在脂多糖诱导的体内外神经炎症中发挥保护作用。

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	周继勤1
	倪玮1
	凌亚亭1
	吕孝瑞1
	牛冬冬1
	曾宇1
	仇昀1
	司雨1
	王子瑜2
	胡嘉波1

关键词 ：神经干细胞, 分泌组, 神经炎症, 小胶质细胞, 表型

Abstract：［Abstract］Objective： To explore the role of neural stem cell secretome (NSC-S) on neuroinflammation in vitro and in vivo and its potential mechanisms. Methods： Mouse models of neuroinflammation were developed by lipopolysaccharide (LPS), the effects of NSC-S on the behavior of mice were evaluated by open-field test, and the effects of NSC-S on the microglia phenotype and neuronal injury of cerebral cortex were assessed by immunofluorescence staining and Nissl staining. BV2 microglial inflammatory model was developed by LPS stimulation in vitro. The effect of NSC-S on the phenotype of BV2 cells was detected by flow cytometry. The antiinflammatory mechanism of NSC-S was studied by using peroxisome proliferator activated receptor-γ (PPAR-γ) inhibitor GW9662. Results： The total distance and average movement speed of the mice treated with NSC-S were significantly increased in the open field test (P<0.05), NSC-S regulated the phenotypic polarization of microglia and inhibited neuronal injury in mouse cortex. In vitro, NSC-S inhibited the expression of M1 surface marker CD86 (P<0.05) and promoted the expression of M2 surface marker CD206 (P<0.01) in BV2 cells, however, GW9662 blocked the regulation effect of NSC-S on BV2 cells phenotypes (P<0.05). Conclusion： NSC-S plays a protective role in LPS-induced neuroinflammation in vivo and in vitro by regulating microglia phenotypes.

收稿日期: 2022-03-26

基金资助:校企协同创新项目(20200605)

通讯作者: 胡嘉波(通讯作者)，教授，博士生导师，E-mail: hu@ujs.edu.cn

作者简介: 周继勤(1996—)，女，硕士研究生；

引用本文:

周继勤1，倪玮1，凌亚亭1，吕孝瑞1，牛冬冬1，曾宇1，仇昀1，司雨1，王子瑜2，胡嘉波1. 神经干细胞分泌组通过调节小胶质细胞表型抑制体内外神经炎症[J]. 江苏大学学报:医学版, 2023, 33(04): 277-283. ZHOU Jiqin1, NI Wei1, LING Yating1, LYU Xiaorui1, NIU Dongdong1, ZENG Yu1, QIU Yun1, SI Yu1, WANG Ziyu2, HU Jiabo1. Neural stem cell secretome inhibited neuroinflammation in vivo and in vitro by regulating microglial phenotypes. Journal of Jiangsu University(Medicine Edition), 2023, 33(04): 277-283.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2023/V33/I04/277

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