[1]闫柳润,龚 婷,方峰杰.IL-37调节Nrf2/NF-κB信号通路对牙周炎大鼠炎症反应的影响[J].陕西医学杂志,2025,54(5):607-611.[doi:DOI:10.3969/j.issn.1000-7377.2025.05.006]
 YAN Liurun,GONG Ting,FANG Fengjie.Effect of IL-37 on inflammatory response in rats with periodontitis via regulation of the Nrf2/NF-κB signaling pathway[J].,2025,54(5):607-611.[doi:DOI:10.3969/j.issn.1000-7377.2025.05.006]
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IL-37调节Nrf2/NF-κB信号通路对牙周炎大鼠炎症反应的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年5期
页码:
607-611
栏目:
基础研究
出版日期:
2025-05-05

文章信息/Info

Title:
Effect of IL-37 on inflammatory response in rats with periodontitis via regulation of the Nrf2/NF-κB signaling pathway
作者:
闫柳润龚 婷方峰杰
(安徽医科大学附属巢湖医院口腔科,安徽 合肥 238000)
Author(s):
YAN LiurunGONG TingFANG Fengjie
(Department of Stomatology,Chaohu Hospital of Anhui Medical University,Hefei 238000,China)
关键词:
牙周炎 白细胞介素-37 核因子E2相关因子2 核因子-κB 炎症反应 大鼠
Keywords:
Periodontitis Interleukin-37 Nuclear factor erythroid 2-related factor 2 Nuclear factor-κB Inflammatory response Rats
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.05.006
文献标志码:
A
摘要:
目的:探讨白细胞介素-37(IL-37)对牙周炎大鼠炎症反应的影响,并初步探讨潜在的作用机制。方法:将30只大鼠随机分为对照组、模型组、IL-37组,每组10只。除对照组外,模型组和IL-37组建立大鼠牙周炎模型。术后每隔1日IL-37组于牙周袋内注射IL-37重组蛋白(1 μg),对照组和模型组同时牙周袋内注射等量0.9%氯化钠溶液。连续干预4周后,对各组大鼠牙龈指数(GI)、龈沟出血指数(SBI)、牙周附着丧失(AL)进行测定; 检测大鼠外周血炎症细胞(白细胞、淋巴细胞、巨噬细胞)数量; ELISA法检测大鼠牙周组织中促炎因子IL-6、IL-8和肿瘤坏死因子-α(TNF-α)水平,抗炎因子IL-37、IL-10表达水平; HE染色观察各组大鼠牙周组织病理学改变; Western blot检测各组大鼠牙周组织中细胞质和细胞核内核因子E2相关因子2(Nrf2)以及核因子-κB(NF-κB)蛋白磷酸化水平。结果:与对照组比较,模型组牙周组织发生明显病理损伤,牙周指标GI、SBI、AL升高; 与模型组比较,IL-37组牙周组织病理损伤明显改善,牙周指标GI、SBI、AL下降(均P<0.05)。与对照组比较,模型组外周血中炎症细胞数量及牙周组织中IL-6、IL-8和TNF-α水平升高,牙周组织中IL-37、IL-10水平降低; 与模型组比较,IL-37组外周血中炎症细胞数量及牙周组织中IL-6、IL-8和TNF-α水平降低,牙周组织中IL-37、IL-10水平升高(均P<0.05)。与对照组比较,模型组细胞核Nrf2蛋白表达水平降低,p-NF-κB p65及细胞质Nrf2蛋白表达水平升高; 与模型组比较,IL-37组细胞核Nrf2蛋白表达水平升高,p-NF-κB p65及细胞质Nrf2蛋白表达水平降低(均P<0.05)。结论:IL-37能减轻牙周炎大鼠牙周炎症反应,改善牙周组织损伤,其作用机制可能与调控Nrf2/NF-κB通路有关。
Abstract:
Objective:To investigate the effect of interleukin-37(IL-37)on inflammatory response in rats with periodontitis and preliminarily explore the underlying mechanisms.Methods:Thirty rats were randomly divided into three groups:control group,model group and IL-37 group,with 10 rats in each group.Except for the control group,periodontitis models were established in the model and IL-37 groups.The IL-37 group received intra-periodontal pocket injections of recombinant IL-37 protein(1 μg)every other day starting from the day after surgery,while the control and model groups received equivalent volumes of 0.9% sodium chloride solution.After 4 weeks of intervention,the gingival index(GI),sulcus bleeding index(SBI),and attachment loss(AL)were measured in each group.The number of peripheral blood inflammatory cells(white blood cells,lymphocytes and macrophages)was determined.Levels of pro-inflammatory cytokines(IL-6,IL-8 and TNF-α)and anti-inflammatory cytokines(IL-37,IL-10)in periodontal tissues were measured using ELISA.Histopathological changes in periodontal tissues were observed by HE staining.The levels of nuclear factor erythroid 2-related factor 2(Nrf2)in the cytoplasm and nucleus of periodontal tissues and the phosphorylation levels of nuclear factor-κB(NF-κB)protein were detected by Western blot.Results:Compared with the control group,the model group exhibited significant pathological damage in periodontal tissues and increased periodontal indices(GI,SBI and AL).Compared with the model group,the IL-37 group showed marked improvement in periodontal tissue damage and decreased periodontal indices(all P<0.05).Compared with the control group,the model group had increased numbers of peripheral blood inflammatory cells and elevated levels of IL-6,IL-8 and TNF-α in periodontal tissues,while IL-37 and IL-10 levels were decreased.In contrast,the IL-37 group had reduced numbers of peripheral blood inflammatory cells and lower levels of IL-6,IL-8 and TNF-α,with increased IL-37 and IL-10 levels in periodontal tissues(all P<0.05).Compared with the control group,the model group exhibited decreased nuclear Nrf2 protein expression and increased p-NF-κB p65 and cytoplasmic Nrf2 protein expression.Compared with the model group,the IL-37 group showed increased nuclear Nrf2 protein expression and decreased p-NF-κB p65 and cytoplasmic Nrf2 protein expression(all P<0.05).Conclusion:IL-37 can alleviate inflammatory response and improve periodontal tissue damage in rats with periodontitis.Its mechanism of action may be related to the regulation of the Nrf2/NF-κB signaling pathway.

参考文献/References:

[1] 王玉玮,李丁新,赵飞,等.熊果酸调控AMPK/SIRT1通路对牙周炎大鼠牙槽骨吸收的影响[J].陕西医学杂志,2023,52(5):517-522.
[2] YE Q,LIN B,XU P,et al.Yunvjian decoction attenuates lipopolysaccharide-induced periodontitis by suppressing NFκB/NLRP3/IL-1β pathway[J].J Ethnopharmacol,2024,319:117279.
[3] 李晋.加味葛根芩连汤联合根面平整术治疗慢性牙周炎临床研究[J].陕西中医,2022,43(7):914-917.
[4] WANG W,LIU Y.Research progress on the immunomodulatory effect of mesenchymal stem cells on chronic periodontitis[J].Open J Stomatol,2024,14(2):8.
[5] 李军,颜杉,许杰,等.IL-37通过调控巨噬细胞极化抑制炎性疾病研究进展[J].现代医药卫生,2023,39(20):3527-3531.
[6] NOLD-PETRY C A,NOLD M F.Rationale for IL-37 as a novel therapeutic agent in inflammation[J].Expert Rev Clin Immunol,2022,18(12):1203-1206.
[7] CAVALLI G,DINARELLO C A.Suppression of inflammation and acquired immunity by IL-37[J].Immunol Rev,2018,281(1):179-190.
[8] SHEN Y,KE X,YUN L,et al.Decreased expression of interleukin-37 and its anti-inflammatory effect in allergic rhinitis[J].Mol Med Rep,2018,17(1):1333-1339.
[9] 张璇.IL-37在牙周组织中的表达[D].济南:山东大学,2013.
[10] 王知刚,胡聪,张波.木犀草素调控OPG对牙周炎大鼠干预效果及作用机制[J].中国老年学杂志,2023,43(24):6025-6028.
[11] 徐娟.牙周基础治疗对侵袭性牙周炎患者唾液和龈沟液中牙周致病菌的作用[J].中外医疗,2016,35(10):25-27.
[12] 吕辰翼,童熹.牙周-牙髓联合病变患者应用中药汤剂联合西医治疗的效果分析[J].中华中医药学刊,2015,33(12):3013-3015.
[13] XU Y,WEI W.A comparative study of systemic subantimicrobial and topical treatment of minocycline in experimental periodontitis of rats[J].Arch Oral Biol,2006,51(9):794-803.
[14] 徐淑云.药理实验方法学[M].3 版.北京:人民卫生出版社,2000:203-204.
[15] KWON T,LAMSTER I B,LEVIN L.Current concepts in the management of periodontitis[J].Int Dent J,2021,71(6):462-476.
[16] NOLD M F,NOLD-PETRY C A,ZEPP J A,et al.IL-37 is a fundamental inhibitor of innate immunity[J].Nat Immunol,2010,11(11):1014-1022.
[17] PAN Y,WEN X,HAO D,et al.The role of IL-37 in skin and connective tissue diseases[J].Biomed Pharmacother,2020,122:109705.
[18] COLL-MIR M,FRANCOS-QUIJORNA I,SANTOS-NOGUEIRA E,et al.Beneficial effects of IL-37 after spinal cord injury in mice[J].Proc Natl Acad Sci U S A,2016,113(5):1411-1416.
[19] MCNAMEE E N,MASTERSON J C,JEDLICKA P,et al.Interleukin 37 expression protects mice from colitis[J].Proc Natl Acad Sci U S A,2011,108(40):16711-16716.
[20] XU D,WANG A,JIANG F,et al.Effects of interleukin-37 on cardiac function after myocardial infarction in mice[J].Int J Clin Exp Pathol,2015,8(5):5247-5251.
[21] KIM D H,KIM S W,KIM S W,et al.Interleukin-37 relieves allergic inflammation in a house dust mite allergic rhinitis murine model[J].Iran J Allergy Asthma Immunol,2017,16(5):404-417.
[22] HUANG Z,GAO C,CHI X,et al.IL-37 expression is upregulated in patients with tuberculosis and induces macrophages towards an M2-like phenotype[J].Scand J Immunol,2015,82(4):370-379.
[23] 刘晓燕,耿文华,杜莎莎,等.龈沟液OPG、IL-35、IL-37在慢性牙周炎中的表达及与牙槽骨吸收的相关性[J].河北医科大学学报,2022,43(9):1068-1072,1078.
[24] JING L,KIM S,SUN L,et al.IL-37- and IL-35/IL-37-producing plasma cells in chronic periodontitis[J].J Dent Res,2019,98(7):813-821.
[25] SAHA S,BUTTARI B,PANIERI E,et al.An overview of Nrf2 signaling pathway and its role in inflammation[J].Molecules,2020,25(22):5474.
[26] SMALE S T.Hierarchies of NF-κB target-gene regulation[J].Nat Immunol,2011,12(8):689-694.
[27] SAKURAI H,SUZUKI S,KAWASAKI N,et al.Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2,TRAF5,and TAK1 signaling pathway[J].J Biol Chem,2003,278(38):36916-36923.
[28] KELEKU-LUKWETE N,SUZUKI M,YAMAMOTO M.An overview of the advantages of Keap1-Nrf2 system activation during inflammatory disease treatment[J].Antioxid Redox Signal,2018,29(17),1746-1755.
[29] PAN H,WANG H,WANG X,et al.The absence of Nrf2 enhances NF-κB-dependent inflammation following scratch injury in mouse primary cultured astrocytes[J].Mediators Inflamm,2012,2012:217580.
[30] WARDYN J D,PONSFORD A H,SANDERSON C M.Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways[J].Biochem Soc Trans,2015,43(4):621-626.
[31] XU Y,LUO Y,WENG Z,et al.Microenvironment-responsive metal-phenolic nanozyme release platform with antibacterial,ROS scavenging,and osteogenesis for periodontitis[J].ACS Nano,2023,17(19):18732-18746.
[32] 毕磊,刘辉,武燃.黄芩素通过Nrf2/NF-κB/NFATc1信号通路对牙周病大鼠破骨细胞形成和牙槽骨吸收的影响[J].广西医学,2021,43(5):600-606.
[33] XU J,HAN X,XIA N,et al.IL-37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway[J].Exp Ther Med,2023,25(6):289.
[34] MENG P,CHEN Z G,ZHANG T T,et al.IL-37 alleviates house dust mite-induced chronic allergic asthma by targeting TSLP through the NF-κB and ERK1/2 signaling pathways[J].Immunol Cell Biol,2019,97(4):403-415.

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备注/Memo

备注/Memo:
[基金项目]安徽省卫生厅医药科研计划项目(11367KJ202101821)
更新日期/Last Update: 2025-05-05