中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (5): 1106-1113.doi: 10.12307/2026.035

• 脊柱组织构建 spinal tissue construction • 上一篇    下一篇

过氧化物还原酶1在脊髓损伤后小胶质细胞炎症反应中的作用及机制

阴勇成1，赵相瑞1，杨志杰2，李  政2，李  芳2，宁  斌2   

  1. 1山东第二医科大学临床医学院，山东省潍坊市   261053；2山东第一医科大学附属中心医院，山东第一医科大学和山东省医学科学院，山东省济南市   250013
  • 收稿日期:2024-11-08 接受日期:2025-01-09 出版日期:2026-02-18 发布日期:2025-06-23
  • 通讯作者: 宁斌，主任医师，山东第一医科大学附属中心医院，山东第一医科大学和山东省医学科学院，山东省济南市 250013
  • 作者简介:阴勇成，男，1997年生，山东省烟台市人，汉族，硕士在读，主要从事脊髓损伤研究。
  • 基金资助:
    国家自然科学基金项目(82071383)，项目负责人：宁斌；山东省自然科学基金项目(ZR2023MH235)，项目负责人：李芳

Effect and mechanism of peroxiredoxin 1 in microglial inflammation after spinal cord injury

Yin Yongcheng1, Zhao Xiangrui1, Yang Zhijie2, Li Zheng2, Li Fang2, Ning Bin2   

  1. 1School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China; 2Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250013, Shandong Province, China
  • Received:2024-11-08 Accepted:2025-01-09 Online:2026-02-18 Published:2025-06-23
  • Contact: Ning Bin, Chief physician, Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250013, Shandong Province, China
  • About author:Yin Yongcheng, MS candidate, School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 82071383 (to NB); Natural Science Foundation of Shandong Province, No. ZR2023MH235 (to LF) 

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摘要：




文题释义：
过氧化物还原酶1：是一种重要的抗氧化酶，属于过氧化物还原酶家族。过氧化物还原酶1主要通过催化过氧化氢和有机过氧化物的还原反应，帮助细胞清除有害的活性氧，保护细胞免受氧化损伤。过氧化物还原酶1在多种生物过程中发挥重要作用，包括细胞增殖、凋亡和信号转导，因此，过氧化物还原酶1不仅在维持细胞氧化还原平衡中起着关键作用，还是潜在的治疗靶点和生物标志物。
活性氧：是细胞代谢过程中产生的一类高度反应性分子，主要包括超氧阴离子、氢过氧化物、羟基自由基和单线态氧等，参与信号转导、免疫反应、氧化应激等过程，在细胞和组织的杀伤作用中发挥了重要作用。

背景：研究表明，小胶质细胞在脊髓损伤后的炎症反应与神经元存活、再生和功能恢复密切相关，过氧化物还原酶1不仅参与氧化应激的调节，还对细胞的增殖、凋亡及炎症反应具有重要影响。
目的：探讨过氧化物还原酶1在脊髓损伤后小胶质细胞炎症反应中的作用及机制。
方法：①将12只C57BL/6小鼠随机分为假手术组(n=6)与脊髓损伤组(n=6)，假手术组不造模，脊髓损伤组采用改进的Allen法构建急性脊髓损伤模型，造模第7天取损伤部位脊髓组织，通过转录组测序筛选差异表达基因，Western blot和RT-qPCR检测过氧化物还原酶1的表达。②将小鼠小胶质细胞BV2分2组处理：对照组经脂多糖刺激6 h，敲除组敲除过氧化物还原酶1 24 h后经脂多糖刺激6 h，RT-qPCR检测过氧化物还原酶1、炎症因子(白细胞介素1β、白细胞介素6、诱导型一氧化氮合成酶、肿瘤坏死因子α、C-C基序趋化因子配体2和C-X-C基序趋化因子配体2)mRNA表达，Western blot检测过氧化物还原酶1、诱导型一氧化氮合成酶与活性氧/丝裂原活化蛋白激酶信号通路蛋白表达。将小鼠小胶质细胞BV2分2组处理：对照组经过氧化氢刺激4 h，敲除组敲除过氧化物还原酶1 24 h后经过氧化氢刺激4 h，2，7-二氯二氢荧光素二乙酸酯探针检测活性氧水平。
结果与结论：①转录组测序、Western blot和RT-qPCR检测结果显示，脊髓损伤组氧化物还原酶1表达高于假手术组(P < 0.05)；②与对照组比较，敲除组过氧化物还原酶1 mRNA与蛋白表达降低(P < 0.05)，白细胞介素1β、白细胞介素6、诱导型一氧化氮合成酶、肿瘤坏死因子α、C-C基序趋化因子配体2和C-X-C基序趋化因子配体2 mRNA表达均升高(P < 0.05)，诱导型一氧化氮合成酶蛋白、p-P38、p-JNK和p-ERK蛋白升高(P < 0.05)，活性氧水平升高(P < 0.05)；③结果表明，过氧化物还原酶1可能通过靶向活性氧/丝裂原活化蛋白激酶信号通路调控小胶质细胞的炎症反应。
https://orcid.org/0009-0000-6120-3854 (阴勇成) 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 脊髓损伤, 过氧化物还原酶1, 小胶质细胞, 活性氧, 炎症, 丝裂原活化蛋白激酶, 工程化组织构建

Abstract: BACKGROUND: The inflammatory response of microglia is closely related to neuronal survival, regeneration, and functional recovery after spinal cord injury. Peroxiredoxin 1 is not only involved in the regulation of oxidative stress, but also has an important effect on cell proliferation, apoptosis, and inflammatory response.
OBJECTIVE: To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.
METHODS: (1) Twelve female C57BL/6 mice were randomly divided into sham-operated (n=6) and spinal cord injury (n=6) groups. The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen’s method. Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes. The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR. (2) Mouse microglia BV2 were divided into two groups: the control group was stimulated with lipopolysaccharide for 6 hours, and in the knockout group, lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells. RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1, inflammatory factors (interleukin 1β, interleukin 6, inducible nitric oxide synthase, tumor necrosis factor α, C-C motif chemokine ligand 2, and C-X-C motif chemokine ligand 2), and western blot was performed to detect the expression of peroxiredoxin 1, inducible nitric oxide synthase, and reactive oxygen/ mitogen-activated protein kinase signaling pathway proteins. Mouse microglia BV2 were treated in two groups: the control group was stimulated by hydrogen peroxide for 4 hours, and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1. The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.
RESULTS AND CONCLUSION: (1) Results from transcriptome sequencing, western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group (P < 0.05). (2) Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein (P < 0.05), increased mRNA expression of interleukin 1β, interleukin 6, inducible nitric oxide synthase, tumor necrosis factor α, C-C motif chemokine ligand 2, and C-X-C motif chemokine ligand 2 (P < 0.05), increased protein expression of inducible nitric oxide synthase, P-P38, P-JNK and P-ERK proteins (P < 0.05), and increased level of reactive oxygen species (P < 0.05). To conclude, peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

Key words: spinal cord injury, peroxiredoxin 1, microglia, reactive oxygen species, inflammation, mitogen-activated protein kinase, engineered tissue construction

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