白细胞介素-37介导炎症反应平衡保护小鼠心肌缺血再灌注损伤的机制

吴帮卫; 孟凯; 赵晓琦; 刘宇宙; 俞坤武; 钟禹成; 吉庆伟; 曾秋棠

doi:10.13201/j.issn.1001-1439.2014.06.020

白细胞介素-37介导炎症反应平衡保护小鼠心肌缺血再灌注损伤的机制

- 1 华中科技大学附属协和医院心内科(武汉, 430022);
- 2 广西壮族自治区人民医院心内科
基金项目:
国家自然科学基金资助项目 (No:81270354, 81160045)

详细信息

通讯作者: 曾秋棠,E-mail:zengqiutang@gmail.com

中图分类号: R542.2

收稿日期: 2014-01-10

Mechanism of interleukin-37 protects against myocardial ischemia/reperfusion injury by balancing inflammatory response in mice

- 1 Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China;
- 2 Department of Cardiology, The people's Hospital of Guangxi Zhuang Autonomous Region

More Information

Corresponding author: ZENG Qiutang, E-mail: zengqiutang@gmail.com

Received Date: 10 January 2014

摘要

摘要: 目的:探讨外源性重组人源性白细胞介素 (IL) -37对小鼠心肌缺血再灌注损伤的影响。方法:8¹0周雄性c57BL/6小鼠为实验对象, 随机分为假手术组、缺血再灌注 (I/R) 对照组和I/R+IL-37干预组, 每组6只。观察各组小鼠I/R后心肌坏死面积及心功能 (24h后), 检测缺血心肌处中性粒细胞募集 (MPO), 以及缺血心肌和血清中肿瘤坏死因子α (TNF-α)、IL-1β、IL-6、IL-10、转化生长因子-β (TGF-β) 表达 (4h后)。结果:与假手术组比较, I/R对照组心功能明显下降, TNF-α、IL-1β和IL-6水平明显增高。IL-37干预组可以明显抑制TNF-α、IL-1β和IL-6表达, 增加IL-10与TGF-β水平, 减轻MPO, 减少心肌坏死面积并改善心功能。结论:IL-37减轻小鼠心肌I/R损伤, 可能与抑制MPO、降低促炎因子表达以及上调抗炎因子表达相关。
- 白细胞介素-37 /
- 缺血再灌注损伤 /
- 中性粒细胞 /
- 炎症反应
Abstract: Objective: To investigate the effect of IL-37on myocardial ischemia/reperfusion injury in mice.Method: Sham or I/R operations were performed on male C57BL/6J mice, and I/R mice were randomly divided intocontrol group and IL-37treated group (each group:n=6).Then the infarct size and cardiac function were detected in 24hours after reperfusion, the MPO activity was measured as an indicator of neutrophil infiltration in the ischemic myocardium 4hours after reperfusion, and the expressions of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and anti-inflammatory cytokines (IL-10, TGF-β) in heart tissue and serum were measured 4hours after reperfusion.Result: Compared with sham group, I/R mice showed a decreased cardiac function accompanying with an increased level of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).However, compared with I/R control mice, IL-37 treated I/R mice significantly reversed the process as demonstrated by reduced infarct size, improved cardiac function, suppressed MPO activity and inflammation response balance characteristic with inhibited pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and improved anti-inflammatory cytokines (IL-10, TGF-β).Conclusion: IL-37 plays a protective role against mouse myocardial I/R injury, suppresses the infiltration of neutrophil towards ischemic myocardium, which may be associated with the balance of inflammation response.
- Interleukin-37 /
- ischemia/reperfusion injury /
- neutrophil /
- inflammation response

HTML全文

参考文献(19)

[1]	YELLON D M, HAUSENLOY D J.Myocardial reperfusion injury[J].N Engl J Med, 2007, 357:1121-1135.
[2]	ARSLAN F, DE KLEIJN D P, PASTERKAMP G.Innate immune signaling in cardiac ischemia[J].Nat Rev Cardiol, 2011, 8:292-300.
[3]	BARTON G M, MEDZHITOV R.Toll-like receptor signaling pathways[J].Science, 2003, 300:1524-1525.
[4]	TETE S, TRIPODI D, ROSATI M, et al.IL-37 (IL-1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation[J].Int J Immunopathol Pharmacol, 2012, 25:31-38.
[5]	NOLD M F, NOLD-PETRY C A, ZEPP J A, et al.IL-37is a fundamental inhibitor of innate immunity[J].Nat Immunol, 2010, 11:1014-1022.
[6]	BULAU A M, FINK M, MAUCKSCH C, et al.In vivo expression of interleukin-37reduceslocalandsystemic inflammation in concanavalinA-inducedhepatitis[J].Sci World J, 2011, 11:2480-2490.
[7]	MCNAMEE E N, MASTERSON J C, JEDLICKA P, et al.Interleukin 37expression protects mice from colitis[J].Proc Natl Acad Sci U S A, 2011, 108:16711-16716.
[8]	SAKAI N, VAN SWERINGEN H L, BELIZAIRE R M, et al.Interleukin-37reduces liver inflammatory injury via effects on hepatocytes and non-parenchymal cells[J].J Gastroenterol Hepatol, 2012, 27:1609-1616.
[9]	Wu B, Zeng Q, Meng K et al.The potential role of IL-37in atherosclerosis.[J].Pharmazie, 2013, 68:857-860.
[10]	KAMINSKI K A, BONDA T A, KORECKI J, et al.Oxidative stress and neutrophil activation——the two keystones of ischemia/reperfusion injury[J].Int J Cardiol, 2002, 86:41-59.
[11]	BOROS P, BROMBERG J S.New cellular and molecular immune pathways in ischemia/reperfusion injury[J].Am J Transplant, 2006, 6:652-658.
[12]	BOYD J H, MATHUR S, WANG Y, et al.Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response[J].Cardiovasc Res, 2006, 72:384-393.
[13]	OYAMA J, BLAIS C JR, LIU X, et al.Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice[J].Circulation, 2004, 109:784-789.
[14]	LI S Z, HONG J, NOLD M F, et al.Recombinant IL-37inhibits LPS induced inflammation in a SIGIRR-and MAPK-dependent manner[abstract] [J].Cytokine, 2013, 63:281-281.
[15]	LI C, ZHAO P, SUN X, et al.Elevated levels of cerebrospinal fluid and plasma interleukin-37in patients with Guillain-Barre syndrome[J].Mediators Inflamm, 2013, 2013:639712.
[16]	FUJITA H, INOUE Y, SETO K, et al.Interleukin-37is elevated in subjects with atopic dermatitis[J].J Dermatol Sci, 2013, 69:173-175.
[17]	SONG L, QIU F, FAN Y, et al.Glucocorticoid regulates interleukin-37in systemic lupus erythematosus[J].J Clin Immunol, 2013, 33:111-117.
[18]	MCCARTNEY-FRANCIS N, JIN W, WAHL S M.Aberrant Toll receptor expression and endotoxin hypersensitivity in mice lacking a functional TGF-beta 1signaling pathway[J].J Immunol, 2004, 172:3814-3821.
[19]	HUANG X, HAZLETT L D, DU W, et al.SIGIRR promotes resistance against Pseudomonas aeruginosa keratitis by down-regulating type-1immunity and IL-1R1 and TLR4 signaling[J].J Immunol, 2006, 177:548-556.