还原型谷胱甘肽对活性氧介导的系统性红斑狼疮患者中性粒细胞NETosis的影响

doi:10.13418/j.issn.1001-165x.2018.05.010

中国临床解剖学杂志 ›› 2018, Vol. 36 ›› Issue (5): 532-535.doi: 10.13418/j.issn.1001-165x.2018.05.010

还原型谷胱甘肽对活性氧介导的系统性红斑狼疮患者中性粒细胞NETosis的影响

廖攀^1,2，　何懿^1,2，　杨方圆^1,2，　庄坚^1,2，　罗贵湖^1,2，　翟泽清^1,2，　孙尔维^1,2

1.南方医科大学第三附属医院风湿免疫科，广州 510630；　2.广东省骨科研究院临床免疫研究所，广州 510630

收稿日期:2018-07-31 出版日期:2018-09-25 发布日期:2018-10-26
通讯作者: 孙尔维，教授，博士生导师，E-mail：sunew@smu.edu.cn
作者简介:廖攀（1989-），硕士，研究方向：固有免疫与自身免疫性疾病，E-mail：277460258@qq.com
基金资助:
国家自然科学基金（81501417, 81671623）

The effect of reduced glutathione on the ROS-mediated NETosis by neutrophils from patients with systemic lupus erythematosus

LIAO Pan ^1,2，HE Yi ^1,2，YANG Fang-yuan ^1,2，ZHUANG Jian ^1,2，LUO Gui-hu ^1,2，ZHAI Ze-qing ^1,2，SUN Er-wei ^1,2

1. Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China; 2. Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, Guangzhou 510630, China

Received:2018-07-31 Online:2018-09-25 Published:2018-10-26

摘要/Abstract

摘要：

目的　探讨抗氧化剂还原型谷胱甘肽（GSH）能否通过调控中性粒细胞ROS水平从而抑制中性粒细胞发生NETosis，减少中性粒细胞胞外诱捕网（neutrophil extracellular traps, NETs）的形成，为临床开发新的治疗系统性红斑狼疮（SLE）的药物提供理论基础。方法　采用梯度离心法分离SLE患者外周血中性粒细胞，利用佛波酯（PMA）诱导中性粒细胞发生NETosis后，检测各组中性粒细胞胞内ROS水平并观察其NETs产生情况。结果　与PMA处理组比较，经过GSH预处理的SLE患者中性粒细胞体外诱导NETs产生明显减少。同时，GSH也能明显降低SLE患者中性粒细胞胞内ROS水平。结论　GSH可能通过调控SLE患者中性粒细胞ROS的水平，从而抑制其发生NETosis，提示GSH可能在SLE治疗中发挥作用。

关键词: 还原型谷胱甘肽, 　系统性红斑狼疮, 　中性粒细胞, 　NETosis, 　活性氧

Abstract:

Objective　Evidence has demonstrated that the formation of neutrophil extracellular traps (NETs) formation mediated by neutrophil plays an important role in the pathogenesis and progression of systemic lupus erythematosus (SLE). In this study, we aimed to investigate whether reduced glutathione (GSH) could decrease the level of intracellular reactive oxygen species (ROS) or inhibit NETs formation. Methods　Neutrophils were isolated from peripheral blood of SLE patients by gradient centrifugation method dextran sedimentation and centrifugation, and then were stimulated with phorbol 12-myristate 13-acetate (PMA). The production of intracellular ROS and the formation of NETs were examined. Results Compared with the PMA group treated with PMA, the group preprocessing with GSH could markedly suppress formation of NET by neutrophils from SLE patients. Moreover, the production of intracellular ROS production was significantly decreased in GSH-treated neutrophils from SLE patients. Conclusion　GSH can significantly inhibit the process of neutrophils' NETosis from SLE patients through modulating the intracellular ROS production. These results indicates that GSH might be a potential therapeutic agent for SLE.

Key words: Reduced glutathione, 　Systemic lupus erythematosus, 　Neutrophils, 　NETosis, 　Reactive oxygen species

廖攀,何懿,杨方圆,庄坚,罗贵湖,翟泽清,孙尔维. 还原型谷胱甘肽对活性氧介导的系统性红斑狼疮患者中性粒细胞NETosis的影响[J]. 中国临床解剖学杂志, 2018, 36(5): 532-535.

LIAO Pan，HE Yi，YANG Fang-yuan，ZHUANG Jian，LUO Gui-hu，ZHAI Ze-qing，SUN Er-wei. The effect of reduced glutathione on the ROS-mediated NETosis by neutrophils from patients with systemic lupus erythematosus[J]. Chinese Journal Of Clinical Anatomy, 2018, 36(5): 532-535.

参考文献

[1] Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria[J]. Science, 2004, 303(5663):1532-1535.
[2] Papayannopoulos V. Neutrophil extracellular traps in immunity and disease[J]. Nat Rev Immunol, 2018, 18(2):134-147.
[3] Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease[J]. Nat Med, 2017, 23(3):279-287.
[4] 谢雅清，梁晓美，叶伟霞. 还原型谷胱甘肽的药理作用与临床应用研究进展[J]. 中国药业, 2013, 22(7):124-127.
[5] 张北平，刘树锋，王海，等. GSH对于系统性红斑狼疮治疗观察[J]. 中国现代药物应用, 2016, 10(13):189-190.
[6] 张均，赵景宏，刘力，等. 还原型谷胱甘肽辅助治疗对狼疮肾炎患者肾小球系膜细胞CXCL9/10/11表达的影响[J]. 中国医学前沿杂志(电子版), 2017, 9(11):118-121.
[7] Domingo-Gonzalez R, Martinez-Colon G J, Smith A J, et al. Inhibition of neutrophil extracellular trap formation after stem cell transplant by prostaglandin E2[J]. Am J Respir Crit Care Med, 2016, 193(2):186-197.
[8] Lood C, Blanco LP, Purmalek MM, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease[J]. Nat Med, 2016, 22(2):146-153.
[9] Hakkim A, Furnrohr BG, Amann K, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis[J]. Proc Natl Acad Sci U S A, 2010,107(21):9813-9818.
[10] Knight JS, Subramanian V, O'Dell AA, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice[J]. Ann Rheum Dis, 2015, 74(12):2199-2206.
[11] Knight JS, Zhao W, Luo W, et al. Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus[J]. J Clin Invest, 2013, 123(7):2981-2993.

还原型谷胱甘肽对活性氧介导的系统性红斑狼疮患者中性粒细胞NETosis的影响

The effect of reduced glutathione on the ROS-mediated NETosis by neutrophils from patients with systemic lupus erythematosus

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

Metrics

本文评价

推荐阅读 0

[1]	姚女兆,唐绍锋,夏曦,谭德容. 活性氧调控因子1在人退变椎间盘中的表达及意义[J]. 中国临床解剖学杂志, 2018, 36(1): 56-60.
[2]	池丹璐，孙煜，潘三强. 樟芝酵素对苯丙胺致PC12细胞毒性损伤的保护作用[J]. 中国临床解剖学杂志, 2017, 35(4): 397-401.