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小胶质细胞的P2X7受体通过调节脊髓损伤后(核苷酸结合寡聚化结构域)样受体蛋白3(NLRP3)炎性小体依赖性炎症介导神经炎症。

P2X7 Receptor (P2X7R) of Microglia Mediates Neuroinflammation by Regulating (NOD)-Like Receptor Protein 3 (NLRP3) Inflammasome-Dependent Inflammation After Spinal Cord Injury.

作者信息

Fan Xiao, Ma Wei, Zhang Yingyu, Zhang Li

机构信息

Qingdao Municipal Hospital, Qingdao, Shandong, China (mainland).

Fujian Universities and Colleges Engineering Research Center of Marine Biopharmaceutical Resources, Xiamen, Fujian, China (mainland).

出版信息

Med Sci Monit. 2020 Sep 21;26:e925491. doi: 10.12659/MSM.925491.

Abstract

BACKGROUND Microglia participate in mediating neuroinflammation in which P2X7R triggered by adenosine triphosphate has a critical effect after spinal cord injury. However, how the P2X7R of microglia regulate neuroinflammation after spinal cord injury is still unclear. The aim of this study was to explore the mechanism by which the P2X7 receptor of microglia regulates neuroinflammation after spinal cord injury in NLRP3 inflammasome-dependent inflammation. MATERIAL AND METHODS Sixt rats were divided into 5 groups: a sham group, a model group, a BzATP group, an A-438079 group, and a BzATP+CY-09 group. Rats in the sham group were only subjected to laminectomy and rats in the other groups were subjected to spinal cord injury followed by treatment with physiological saline, BzATP, A-438079, and BzATP following CY-09, separately. Real-time polymerase chain reaction, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to analyze the scientific hypothesis. RESULTS (i) P2X7R of microglia was upregulated and downregulated by BzATP, and A-438079 was upregulated after spinal cord injury. (ii) Upregulation of P2X7R on microglia is coincident with increase of neuroinflammation after spinal cord injury. (iii) P2X7R of microglia participates in spinal cord-mediated neuroinflammation via regulating NLRP3 inflammasome-dependent inflammation. CONCLUSIONS P2X7R of microglia in spinal cord mediates neuroinflammation by regulating NLRP3 inflammasome-dependent inflammation after spinal cord injury.

摘要

背景

小胶质细胞参与介导神经炎症,其中三磷酸腺苷触发的P2X7受体在脊髓损伤后具有关键作用。然而,脊髓损伤后小胶质细胞的P2X7受体如何调节神经炎症仍不清楚。本研究的目的是探讨在NLRP3炎性小体依赖性炎症中,小胶质细胞的P2X7受体调节脊髓损伤后神经炎症的机制。

材料与方法

将60只大鼠分为5组:假手术组、模型组、BzATP组、A-438079组和BzATP+CY-09组。假手术组大鼠仅接受椎板切除术,其他组大鼠接受脊髓损伤,然后分别用生理盐水、BzATP、A-438079和CY-09后的BzATP进行治疗。采用实时聚合酶链反应、蛋白质免疫印迹法、免疫荧光染色和酶联免疫吸附测定法分析科学假设。

结果

(i)脊髓损伤后,小胶质细胞的P2X7R被BzATP上调和下调,A-438079被上调。(ii)小胶质细胞上P2X7R的上调与脊髓损伤后神经炎症的增加一致。(iii)小胶质细胞的P2X7R通过调节NLRP3炎性小体依赖性炎症参与脊髓介导的神经炎症。

结论

脊髓中小胶质细胞的P2X7R通过调节脊髓损伤后NLRP3炎性小体依赖性炎症介导神经炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58bf/7518010/8092115e02b2/medscimonit-26-e925491-g001.jpg

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