抑制MIF活性对大鼠种植体周围炎骨吸收的影响

doi:10.13591/j.cnki.kqyx.2026.05.005

摘要/Abstract

摘要：

目的探究抑制巨噬细胞移动抑制因子（macrophage migration inhibitory factor，MIF）活性对种植体周围炎骨吸收的影响。方法将20只雄性SD大鼠随机分为空白对照组、炎症对照组、炎症治疗组、炎症溶剂组4组。拔除每只大鼠双侧第一磨牙后，即刻植入钛合金皮质骨螺钉。所有炎症组大鼠以丝线结扎种植体的方式构建种植体周围炎模型。随后，空白对照组与炎症对照组大鼠的种植体周围牙龈注射生理盐水，炎症治疗组注射MIF抑制剂ISO-1，炎症溶剂组注射二甲基亚砜（dimethyl sulfoxide，DMSO）溶液。Micro-CT扫描观察各组种植体周围骨吸收情况，分析骨密度及骨体积分数；HE染色观察种植体周围组织的组织学表现；免疫组化分析IL-6、IL-10的蛋白表达水平。结果与空白对照组相比，3个炎症组的骨密度及骨体积分数明显降低（P<0.05）；HE染色可见炎细胞浸润及纤维结缔组织形成；IL-6、IL-10的表达水平升高（P<0.05）；在局部抑制MIF的活性后，与炎症对照组和炎症溶剂组相比，炎症治疗组的骨密度及骨体积分数增加，IL-6的表达降低，IL-10的表达增加（P<0.05）。结论抑制MIF活性可减轻种植体周围炎的骨吸收，其机制可能与IL-6表达降低同时IL-10表达升高有关。

关键词: 种植体周围炎, 巨噬细胞移动抑制因子, ISO-1, IL-6, IL-10

Abstract:

Objective To investigate the effect of inhibiting macrophage migration inhibitory factor（MIF） activity on bone resorption in rat peri-implantitis. Methods Twenty male Sprague-Dawley（SD） rats were randomly divided into four groups： blank control group，inflammation control group，inflammation treatment group，and inflammation solvent group. After extracting the bilateral first molars of each rat，titanium alloy cortical bone screws were immediately implanted. In all inflammation groups，peri-implantitis models were constructed by ligating the implants with silk thread. Subsequently，the peri-implant gingiva of rats in the blank control group and inflammation control group was injected with normal saline； the inflammation treatment group was injected with MIF inhibition ISO-1，and the inflammation solvent group was injected with dimethyl sulfoxide（DMSO） solution. Micro-CT scanning was used to observe the peri-implant bone resorption，and analyze bone mineral density（BMD） and bone volume fraction（BV/TV）. HE staining was performed to observe the histological manifestations of peri-implant tissues. Immunohistochemical analysis was used to detect the protein expression levels of IL-6 and IL-10. Results Compared with the blank control group，the BMD and BV/TV in the three inflammation groups were significantly decreased（P<0.05）； HE staining showed inflammatory cell infiltration and fibrous connective tissue formation； the expression levels of IL-6 and IL-10 were increased（P<0.05）. After local inhibition of MIF activity，compared with the inflammation control group and inflammation solvent group，the inflammation treatment group showed increased BMD and BV/TV，decreased IL-6 expression，and increased IL-10 expression（P<0.05）. Conclusion Inhibition of MIF activity can alleviate bone loss in peri-implantitis，and the mechanism may be related to the decrease in IL-6 expression and the increase in IL-10 expression.

Key words: peri-implantitis, macrophage migration inhibitory factor, ISO-1, IL-6, IL-10

中图分类号:

R782.13

高菁哲, 曹嘉骏, 李海旭, 孙宇. 抑制MIF活性对大鼠种植体周围炎骨吸收的影响[J]. 口腔医学, 2026, 46(5): 350-355.

GAO Jingzhe, CAO Jiajun, LI Haixu, SUN Yu. The effect of inhibiting MIF activity on bone resorption in rat peri-implantitis[J]. Stomatology, 2026, 46(5): 350-355.

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参考文献 28

[1]	赵铱民. 口腔修复学[M]. 8版. 北京: 人民卫生出版社, 2020.
[2]	Diaz P, Gonzalo E, Villagra LJG, et al. What is the prevalence of peri-implantitis? A systematic review and meta-analysis[J]. BMC Oral Health, 2022, 22(1): 449.
[3]	Karlsson K, Derks J, Wennström JL, et al. Health economic aspects of implant-supported restorative therapy[J]. Clin Oral Implants Res, 2022, 33(2): 221-230.
[4]	宋应亮, 张思佳. 对种植体周围炎的认识与预防[J]. 华西口腔医学杂志, 2020, 38(5): 479-483.
[5]	李阳, 胡晓潘, 聂红兵, 等. 种植体周围炎的影响因素及临床防治措施[J]. 西北民族大学学报(自然科学版), 2023, 44(4): 21-25.
[6]	Bucala R, Donnelly SC. Macrophage migration inhibitory factor: A probable link between inflammation and cancer[J]. Immunity, 2007, 26(3): 281-285.
[7]	Ortiz-García YM, García-Iglesias T, Morales-Velazquez G, et al. Macrophage migration inhibitory factor levels in gingival crevicular fluid, saliva, and serum of chronic periodontitis patients[J]. Biomed Res Int, 2019, 2019: 7850392.
[8]	Yilmaz D, Gönüllü E, Gürsoy M, et al. Salivary and serum concentrations of monocyte chemoattractant protein-1, macrophage inhibitory factor, and fractalkine in relation to rheumatoid arthritis and periodontitis[J]. J Periodontol, 2021, 92(9): 1295-1305.
[9]	Pakozdi A, Amin MA, Haas CS, et al. Macrophage migration inhibitory factor: A mediator of matrix metalloproteinase-2 production in rheumatoid arthritis[J]. Arthritis Res Ther, 2006, 8(4): R132.
[10]	Kensara A, Hefni E, Williams MA, et al. Microbiological profile and human immune response associated with peri-implantitis: A systematic review[J]. J Prosthodont, 2021, 30(3): 210-234.
[11]	Al-Sabbagh M, Shaddox LM. Is peri-implantitis curable?[J]. Dent Clin North Am, 2019, 63(3): 547-566.
[12]	Alves CH, Russi KL, Rocha NC, et al. Host-microbiome interactions regarding peri-implantitis and dental implant loss[J]. J Transl Med, 2022, 20: 425.
[13]	Fang TF, Liu L, Song DZ, et al. The role of MIF in periodontitis: A potential pathogenic driver, biomarker, and therapeutic target[J]. Oral Dis, 2024, 30(3): 921-937.
[14]	Gazar Y, Hanafy M, Elrefi M. ab0076 the role of macrophage migration inhibitory factor inactivity and progression of ankylosing spondylitis[J]. Ann Rheum Dis, 2021, 80: 1068.
[15]	Huang MS, Wang C, Li P, et al. Role of immune dysregulation in peri-implantitis[J]. Front Immunol, 2024, 15: 1466417.
[16]	Madeira MFM, Queiroz-Junior CM, Costa GM, et al. MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice[J]. Microbes Infect, 2012, 14(2): 198-206.
[17]	Kim H, Ahn SH, Shin C, et al. The association of higher plasma macrophage migration inhibitory factor levels with lower bone mineral density and higher bone turnover rate in postmenopausal women[J]. Endocrinol Metab (Seoul), 2016, 31(3): 454-461.
[18]	Onodera S, Sasaki S, Ohshima S, et al. Transgenic mice overexpressing macrophage migration inhibitory factor (MIF) exhibit high-turnover osteoporosis[J]. J Bone Miner Res, 2006, 21(6): 876-885.
[19]	Oner F, Onat FC, Ozkan Karasu Y. Salivary and serum nitric oxide synthase, macrophage inflammatory protein 1 alpha and macrophage migration inhibitory factor levels in periodontal disease[J]. Heliyon, 2024, 10(4): e25888.
[20]	孟令玮, 李雪, 高胜寒, 等. 三种方法建立大鼠种植体周炎模型的比较[J]. 北京大学学报(医学版), 2023, 55(1): 22-29.
[21]	喻莉, 许益萌, 杨一帆. 种植体周围龈沟液中IL-6、CRP及氧化应激标志物水平与种植体周围炎的关系[J]. 检验医学与临床, 2021, 18(21): 3153-3156.
[22]	魏洁雅, 徐思群, 周学东, 等. 牙槽骨修复重建分子调控机制的研究新进展[J]. 四川大学学报(医学版), 2024, 55(1): 31-38.
[23]	刘静, 姜明霞. 炎症细胞因子IL-1β和IL-6在老年2型糖尿病合并骨质疏松患者血清中的表达及临床意义[J]. 中国老年学杂志, 2024, 44(3): 590-593.
[24]	门贝, 朱燕. IL-6抑制剂对种植体周围炎小鼠模型的疗效及其作用机制探讨[J]. 中国美容医学, 2022, 31(5): 90-93.
[25]	Liu YY, Liu YN, Wang QF, et al. MIF inhibitor ISO-1 alleviates severe acute pancreatitis-associated acute kidney injury by suppressing the NLRP3 inflammasome signaling pathway[J]. Int Immunopharmacol, 2021, 96: 107555.
[26]	Xie K, Chai YS, Lin SH, et al. Luteolin regulates the differentiation of regulatory T cells and activates IL-10-dependent macrophage polarization against acute lung injury[J]. J Immunol Res, 2021, 2021: 8883962.
[27]	Relvas M, Mendes-Frias A, Gonçalves M, et al. Salivary IL-1β, IL-6, and IL-10 are key biomarkers of periodontitis severity[J]. Int J Mol Sci, 2024, 25(15): 8401.
[28]	Chen XT, Wan Z, Yang L, et al. Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA[J]. J Nanobiotechnology, 2022, 20(1): 110.

组别	BV/TV	BMD/（g/cm³）
空白对照组	0.82±0.06^#	1.10±0.07^#
炎症对照组	0.46±0.12^*#	0.46±0.11^*#
炎症治疗组	0.64±0.17^*	0.82±0.11^*
炎症溶剂组	0.45±0.20^*#	0.62±0.16^*#

组别	IL-6/%	IL-10/%
空白对照组	1.52±0.96^#	3.39±1.68^#
炎症对照组	8.47±3.05^*#	8.95±1.83^*#
炎症治疗组	5.13±1.01^*	14.51±6.39^*
炎症溶剂组	8.88±3.26^*#	8.97±3.28^*#