靶向抑制NLRP3炎性小体在脊髓损伤中的研究进展

doi:10.11958/20221718

天津医药 ›› 2023, Vol. 51 ›› Issue (7): 781-784.doi: 10.11958/20221718

• 综述 • 上一篇

靶向抑制NLRP3炎性小体在脊髓损伤中的研究进展

朱晶惠(), 魏栋敏, 任淑婷, 杨彦玲, 赵琳()

延安大学医学院（邮编716000）

收稿日期:2022-11-01 修回日期:2023-03-03 出版日期:2023-07-15 发布日期:2023-07-18
通讯作者: ^△赵琳 E-mail:jkpzhaolin@163.com
作者简介:朱晶惠（1994），女，硕士在读，主要从事脊髓损伤与再生方面研究。E-mail：1045868672@163.com
基金资助:
国家自然科学基金资助项目(81641048);国家自然科学基金资助项目(81760235);陕西省科技厅社会发展领域项目(2021SF-082)

Research progress of targeted inhibition of NLRP3 inflammasome in spinal cord injury

ZHU Jinghui(), WEI Dongmin, REN Shuting, YANG Yanling, ZHAO Lin()

Medical College of Yan'an University, Yan'an 716000, China

Received:2022-11-01 Revised:2023-03-03 Published:2023-07-15 Online:2023-07-18
Contact: ^△ZHAO Lin E-mail:jkpzhaolin@163.com

朱晶惠, 魏栋敏, 任淑婷, 杨彦玲, 赵琳. 靶向抑制NLRP3炎性小体在脊髓损伤中的研究进展[J]. 天津医药, 2023, 51(7): 781-784.

ZHU Jinghui, WEI Dongmin, REN Shuting, YANG Yanling, ZHAO Lin. Research progress of targeted inhibition of NLRP3 inflammasome in spinal cord injury[J]. Tianjin Medical Journal, 2023, 51(7): 781-784.

摘要/Abstract

摘要：

脊髓损伤（SCI）是一种难以治愈的神经创伤性疾病，常见病因包括高空坠落、交通事故和重物砸伤等。炎症反应是机体在遭遇外界刺激时产生的免疫保护防线，适当的炎症反应可保护机体免受内外源性侵害。核苷酸结合寡聚结构域样受体蛋白3（NLRP3）炎性小体作为目前研究最多的炎性小体，研究发现其在SCI后表达量显著增加，并介导炎症级联反应。该文就NLRP3的激活机制及脊髓损伤后靶向抑制NLRP3激活机制的相关措施进行综述。

关键词: 脊髓损伤, NLR家族, 热蛋白结构域包含蛋白3, 炎症

Abstract:

Spinal cord injury (SCI) is a neurotraumatic disease that is difficult to cure, and common causes include falling from height, traffic accident and heavy object injury. Inflammatory response is an immune protection produced by body in response to external stimuli. Appropriate inflammatory response can protect body from endogenous and external damage. The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, as the most studied inflamolosome, has significantly increased expression after SCI and mediates the inflammatory cascade. This article reviews the activation mechanism of NLRP3 and relevant measures to inhibit the activation mechanism of NLRP3 after SCI.

Key words: spinal cord injury, NLR family, pyrin domain-containing 3 protein, inflammation

中图分类号:

R322.8

图/表 1

参考文献 39

[1]	MAKONI N J, NICHOLS M R. The intricate biophysical puzzle of caspase-1 activation[J]. Arch Biochem Biophys, 2021, 699:108753. doi:10.1016/j.abb.2021.108753.
[2]	COLLl R C, SCHRODER K, PELEGRIN P. NLRP3 and pyroptosis blockers for treating inflammatory diseases[J]. Trends Pharmacol Sci, 2022, 43(8):653-668. doi:10.1016/j.tips.2022.04.003.
[3]	BLEVINS H M, XU Y, BIBY S, et al. The NLRP3 inflammasome pathway:A review of mechanisms and inhibitors for the treatment of inflammatory diseases[J]. Front Aging Neurosci, 2022, 14:879021. doi:10.3389/fnagi.2022.879021.
[4]	LI Y, XIA Y, YIN S, et al. Targeting microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 inflammasome axis in Parkinson's disease[J]. Front Immunol, 2021, 12:719807. doi:10.3389/fimmu.2021.719807.
[5]	LI C, CHEN M, HE X, et al. A mini-review on ion fluxes that regulate NLRP3 inflammasome activation[J]. Acta Biochim Biophys Sin(Shanghai), 2021, 53(2):131-139. doi:10.1093/abbs/gmaa155.
[6]	SEOK J K, KANG H C, CHO Y Y, et al. Regulation of the NLRP3 inflammasome by post-translational modifications and small molecules[J]. Front Immunol, 2020, 11:618231. doi:10.3389/fimmu.2020.618231.
[7]	AI MAMUN A, WU Y, MONALISA I, et al. Role of pyroptosis in spinal cord injury and its therapeutic implications[J]. J Adv Res, 2021, 28:97-109. doi:10.1016/j.jare.2020.08.004.
[8]	季英楠, 东黎阳, 冯时. 白三烯受体拮抗剂孟鲁司特对脊髓损伤大鼠的神经保护作用及可能机制[J]. 解剖科学进展, 2021, 27(6):709-712.
	JI Y N, DONG L Y, FENG S. Neuroprotective effect of leukotriene receptor antagonist montelukast on rats with spinal cord injury and its possible mechanism[J]. Progress of Anatomical Sciences, 2021, 27(6):709-712. doi:10.16695/j.cnki.10062947.2021.06.018.
[9]	LI Y, LEI Z, RITZEL R M, et al. Impairment of autophagy after spinal cord injury potentiates neuroinflammation and motor function deficit in micet[J]. Theranostics, 2022, 12(12):5364-5388. doi:10.7150/thno.72713.
[10]	ZHAO H, WANG X, LIU S, et al. Paeonol regulates NLRP3 inflammasomes and pyroptosis to alleviate spinal cord injury of rat[J]. BMC Neurosci, 2022, 23(1):16. doi:10.1186/s12868-022-00698-9.
[11]	LIU Z, YAO X, SUN B, et al. Pretreatment with kaempferol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury[J]. Free Radic Biol Med, 2021, 168:142-154. doi:10.1016/j.freeradbiomed.2021.03.037.
[12]	GUO R, GAO S, FENG Y, et al. Ulinastatin attenuates spinal cord injury by targeting AMPK/NLRP3 signaling pathway[J]. J Chem Neuroanat, 2022, 125:102145. doi:10.1016/j.jchemneu.2022.102145.
[13]	GAO S, XU T, GUO H, et al. Ameliorative effects of echinacoside against spinal cord injury via inhibiting NLRP3 inflammasome signaling pathway[J]. Life Sci, 2019, 237:116978. doi:10.1016/j.lfs.2019.116978.
[14]	DAI W, WANG X, TENG H, et al. Celastrol inhibits microglial pyroptosis and attenuates inflammatory reaction in acute spinal cord injury rats[J]. Int immunopharmacol, 2019, 66:215-223. doi:10.1016/j.intimp.2018.11.029.
[15]	邹佳芮, 霍晓蓓, 常毅, 等. 长托宁介导NLRP3炎性小体调控IKKβ/IKKα/NF-κB通路抑制脊髓损伤大鼠细胞焦亡[J]. 解剖科学进展, 2022, 28(2):121-124,128.
	ZOU J R, HUO X B, CHANG Y, et al. Penehyclidine hydrochloride mediates NLRP3 inflammatory corpuscles to regulate IKKβ/IKKα/NF-κB pathway to inhibit pyrolysis of spinal cord injury rats[J]. Progress of Anatomical Sciences, 2022, 28(2):121-124,128. doi:10.16695/j.cnki.1006-2947.2022.02.003.
[16]	QIU Y, HUANG Y, CHEN M, et al. Mitochondrial DNA in NLRP3 inflammasome activation[J]. Int Immunopharmacol, 2022, 108:108719. doi:10.1016/j.intimp.2022.108719.
[17]	QAYYUM N, HASEEB M, KIM M S, et al. Role of thioredoxin-interacting protein in diseases and its therapeutic outlook[J]. Int J M Sci, 2021, 22(5):2754. doi:10.3390/ijms22052754.
[18]	蒋伟宇, 胡旭栋, 陈云琳, 等. 白藜芦醇抑制脊髓损伤兔的NLRP3炎症小体活化[J]. 中国临床药理学与治疗学, 2020, 25(8):850-856.
	JING W Y, HU X D, CHEN Y L, et al. Esveratrol inhibits NLRP3 inflammasome activation in rabbits with spinal cord injury[J]. Chin J Clin Pharmacol Ther, 2020, 25(8):850-856. doi:10.12092/j.issn.1009-2501.2020.08.002.
[19]	王臣健, 陈春晓, 徐涛, 等. 阿魏酸钠对大鼠脊髓损伤中NLRP3炎性小体的影响及机制[J]. 中国脊柱脊髓杂志, 2021, 31(8):739-748.
	WANG C J, CHEN C X, XU T, et al. Effect and mechanism of sodium ferulate on NLRP3 inflammasomes in spinal cord injury[J]. Chinese Journal of Spine and Spinal Cord, 2021, 31(8):739-748. doi:10.3969/j.issn.1004-406X.2021.08.09.
[20]	吴兵, 生梦飞, 张想旺, 等. 木犀草素对脊髓损伤大鼠 Nrf2/HO-1通路的影响[J]. 中国药师, 2021, 24(10):1833-1837.
	WU B, SHENG M F, ZHANG X W, et al. Effects of luteolin on Nrf2/HO-1 pathway in rats with spinal cord injury[J]. China Pharmacist, 2021, 24(10):1833-1837. doi:10.19962/j.cnki.issn1008-049X.2021.10.011.
[21]	LIN Z H, WANG S Y, CHEN L L, et al. Methylene blue mitigates acute neuroinflammation after spinal cord injury through inhibiting NLRP3 inflammasome activation in microglia[J]. Front Cell Neurosci, 2017, 11:391. doi:10.3389/fncel.2017.00391.
[22]	MOHAMED I N, LI L, ISMAEL S, et al. Thioredoxin interacting protein,a key molecular switch between oxidative stress and sterile inflammation in cellular response[J]. World J Diabetes, 2021, 12(12):1979-1999. doi:10.4239/wjd.v12.i12.1979.
[23]	WANG S, WANG B, SHANG D, et al. Ion channel dysfunction in astrocytes in neurodegenerative diseases[J]. Front physiol, 2022, 13:814285. doi:10.3389/fphys.2022.814285.
[24]	LIU G, CHEN X, WANG Q, et al. NEK7:A potential therapy target for NLRP3-related diseases[J]. Biosci Trends, 2020, 14(2):74-82. doi:10.5582/bst.2020.01029.
[25]	WANG L, NEGRO R, WU H. TRPM2,linking oxidative stress and Ca²⁺ permeation to NLRP3 inflammasome activation[J]. Curr Opin Immunol, 2020, 62:131-135. doi:10.1016/j.coi.2020.01.005.
[26]	ABUAMMAR H, BHATTACHARJEE A, SIMON-VECSEI Z, et al. Ion channels and pumps in autophagy:A reciprocal relationship[J]. Cells, 2021, 10(12):3537. doi:10.3390/cells10123537.
[27]	KONG G, LIU J, LI R, et al. Ketone metabolite β-hydroxybutyrate ameliorates inflammation after spinal cord injury by inhibiting the NLRP3 inflammasome[J]. Neurochem Res, 2021, 46(2):213-229. doi:10.1007/s11064-020-03156-2.
[28]	LIN F, LIU Y, LUO W, et al. Minocycline-loaded poly(α-lipoic acid)-methylprednisolone prodrug nanoparticles for the combined anti-inflammatory treatment of spinal cord injury[J]. Int J Nanomedicine, 2022, 17:91-104. doi:10.2147/IJN.S344491.
[29]	FANG Y, HUANG X, WAN Y, et al. Deficiency of TREK-1 potassium channel exacerbates secondary injury following spinal cord injury in mice[J]. J Neurochem, 2017, 141(2):236-246. doi:10.1111/jnc.13980.
[30]	付健, 许伟, 魏浩飞, 等. 木犀草素对大鼠脊髓缺血再灌注损伤的修复作用及机制[J]. 脑与神经疾病杂志, 2019, 27(9):552-556.
	FU J, XU W, WEI H F, et al. Protection of luteolin on spinal cord ischemia-reperfusion injury in rats[J]. Journal of Brain and Nervous Diseases, 2019, 27(9):552-556.
[31]	WU Q, ZHANG Y, ZHANG Y, et al. Riluzole improves functional recovery after acute spinal cord injury in rats and may be associated with changes in spinal microglia/macrophages polarization[J]. Neurosci Lett, 2020, 723:134829. doi:10.1016/j.neulet.2020.134829.
[32]	CHEVRIAUX A, PILOT T, DERANGÈRE V, et al. Cathepsin B is required for NLRP3 inflammasome activation in macrophages,through NLRP3 interaction[J]. Front Cell Dev Biol, 2020, 8:167. doi:10.3389/fcell.2020.00167.
[33]	LI Y, JONES J W, M C CHOI H, et al. cPLA2 activation contributes to lysosomal defects leading to impairment of autophagy after spinal cord injury[J]. Cell Death Dis, 2019, 10(7):531. doi:10.1038/s41419-019-1764-1.
[34]	YOON M C, CHRISTY M P, PHAN V V, et al. Molecular features of CA-074 pH-dependent inhibition of cathepsin B[J]. Biochemistry, 2022, 61(4):228-238. doi:10.1021/acs.biochem.1c00684.
[35]	AMO-APARICIO J, GARCIA-GARCIA J, PUIGDOMENECH M, et al. Inhibition of the NLRP3 inflammasome by OLT1177 induces functional protection and myelin preservation after spinal cord injury[J]. Exp Neurol, 2022, 347:113889. doi:10.1016/j.expneurol.2021.113889.
[36]	CHENG J, HAO J, JIANG X, et al. Ameliorative effects of miR-423-5p against polarization of microglial cells of the M1 phenotype by targeting a NLRP3 inflammasome signaling pathway[J]. Int Immunopharmacol, 2021, 99:108006. doi:10.1016/j.intimp.2021.108006.
[37]	HONG Z, CHENG J, YE Y, et al. MicroRNA-451 attenuates the inflammatory response of activated microglia by downregulating nucleotide binding oligomerization domain-like receptor protein 3[J]. World Neurosurg, 2022, 167:1128-1137. doi:10.1016/j.wneu.2022.08.139.
[38]	LI H, GUAN Y, LIANG B, et al. Therapeutic potential of MCC950,a specific inhibitor of NLRP3 inflammasome[J]. Eur J Pharmacol, 2022, 928:175091. doi:10.1016/j.ejphar.2022.175091.
[39]	JIANG W, LI M, HE F, et al. Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice[J]. J Neuroinflammation, 2017, 14(1):207. doi:10.1186/s12974-017-0980-9.

靶向抑制NLRP3炎性小体在脊髓损伤中的研究进展

Research progress of targeted inhibition of NLRP3 inflammasome in spinal cord injury

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 1

参考文献 39

相关文章 15

编辑推荐

Metrics

本文评价

[1]	陈晶晶, 农章嵩, 谭良源, 杨培培, 梁英业, 唐宏亮, 王开龙. 小胶质细胞极化在神经病理性疼痛中作用研究进展[J]. 天津医药, 2024, 52(9): 1000-1003.
[2]	范慧慧, 任玉梅, 田新磊, 张凯, 李晓丽. 止咳平喘方对支气管哮喘小鼠气道炎症及TLR4/TRAF6/NF-κB通路的影响[J]. 天津医药, 2024, 52(9): 924-929.
[3]	贾维宁, 鲍亚玲, 雷慧, 殷晓宁. 夏枯草提取物对脓毒症小鼠炎症反应和腹腔巨噬细胞的影响[J]. 天津医药, 2024, 52(9): 930-935.
[4]	李大强, 李坚, 陆哲明, 曹阳. 毛蕊异黄酮对脊髓损伤大鼠神经元自噬及凋亡的影响[J]. 天津医药, 2024, 52(8): 798-803.
[5]	吴波, 朱卓农, 郑丽娟, 陈俊如. 苦参碱对特应性皮炎炎症、氧化应激和伤口愈合的影响[J]. 天津医药, 2024, 52(6): 566-571.
[6]	袁满, 冯子瀚, 谢敏, 王柏军. 大黄素对骨关节炎模型小鼠痛觉行为的调节机制[J]. 天津医药, 2024, 52(6): 572-577.
[7]	蒋韬, 程红艳, 吴琼. 棕矢车菊素调节SDF-1α/CXCR4信号通路对妊娠糖尿病大鼠炎症反应的影响[J]. 天津医药, 2024, 52(6): 594-598.
[8]	霍晶辰, 王悦, 李华, 邱嵘, 苏景伟, 王卓凡, 杨洁. 系统免疫炎症指数对根治性放疗Ⅲ期肺鳞癌患者长期生存的预测价值[J]. 天津医药, 2024, 52(6): 634-638.
[9]	慕静然, 骆延, 梁璇, 徐陶, 曾俊伟, 刘晓红. 补体系统激活参与阿尔茨海默病的研究进展[J]. 天津医药, 2024, 52(6): 663-668.
[10]	韩正怡, 李锐, 陈齐, 王家友, 盛奎, 宋洁, 张野. 收肌管阻滞联合全麻对老年全膝关节置换术患者术后疼痛和认知功能的影响[J]. 天津医药, 2024, 52(5): 523-527.
[11]	吕梦娜, 李建斌, 吴锐. 自身炎症性疾病患者合并COVID-19严重程度的早期预测指标探讨[J]. 天津医药, 2024, 52(5): 528-531.
[12]	贾西瑞, 刘莉洁. 小胶质细胞在脓毒症相关性脑病中的作用及研究进展[J]. 天津医药, 2024, 52(5): 557-560.
[13]	王月, 权兴苗, 王玉, 宋春侠, 邵月, 徐立伟. 益气升清方调节HIF-1α/NLRP3信号通路对缺血性脑卒中大鼠神经元焦亡的影响[J]. 天津医药, 2024, 52(4): 350-355.
[14]	何亚男, 蔡翔, 邱百怡, 孙邦梅, 李伶华. 穿心莲内酯调节cGAS-STING信号通路对银屑病小鼠的治疗作用[J]. 天津医药, 2024, 52(4): 379-386.
[15]	吴倩, 王意, 陈念, 周凯, 田昕, 徐晖, 苟小霞. 诱导化疗对鼻咽癌患者免疫功能及炎症指标的影响[J]. 天津医药, 2024, 52(4): 397-402.