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建立双小鼠模型以探究小鼠糖尿病与牙周炎之间的相互作用。

Establishing a Dual Murine Model to Explore the Interactions Between Diabetes and Periodontitis in Mice.

作者信息

Silva Bárbara R, Hidalgo Marco A R, Silva Renata C L, de Avila Erica D, Fuentes Deivys L P, Carlos Iracilda Z, Figueiredo Ingrid D, Cerri Estela S, Cerri Paulo S, Baviera Amanda M, de Molon Rafael Scaf, Scarel-Caminaga Raquel M

机构信息

Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil.

Department of Diagnosis and Surgery, School of Dentistry at Araçatuba, Sao Paulo State University-UNESP, Araçatuba 16015-050, SP, Brazil.

出版信息

Int J Mol Sci. 2025 Jun 11;26(12):5611. doi: 10.3390/ijms26125611.

DOI:10.3390/ijms26125611
PMID:40565075
Abstract

This study aimed to develop and validate a dual murine model integrating a high-fat diet (HFD) and a single streptozotocin (STZ) dose to induce diabetes mellitus (DM), alongside periodontitis (Perio) induced by ligature placement and oral inoculation with (). The goal was to mimic human pathological conditions, creating a physiologically relevant environment to study the interplay between DM and Perio. A total of 128 six-week-old male C57BL/6J mice were randomly divided into four groups: Control, DM, Perio, and DM-P. DM was induced by HFD and STZ injection, and Perio by ligature placement and infection. Evaluations occurred at baseline and days 7, 14, and 21. Alveolar bone loss was assessed by micro-computed tomography, and inflammation was examined histologically. DM mice showed elevated glucose levels and insulin resistance. Perio and DM-P groups experienced significant bone loss compared with Control and DM groups. The morphometric analysis revealed abundant inflammatory cells and reduced collagen fibers in Perio and DM-P groups, especially at day 7. This dual murine model successfully replicated the key features of DM and Perio, maintaining overall health of the animals, and good tolerability by those subjects to the stress of both interventional procedures.

摘要

本研究旨在建立并验证一种双鼠模型,该模型整合了高脂饮食(HFD)和单次链脲佐菌素(STZ)剂量以诱导糖尿病(DM),同时通过结扎和口腔接种()诱导牙周炎(Perio)。目的是模拟人类病理状况,创建一个生理相关环境来研究DM和Perio之间的相互作用。总共128只六周龄雄性C57BL/6J小鼠被随机分为四组:对照组、DM组、Perio组和DM-P组。通过HFD和注射STZ诱导DM,通过结扎和感染诱导Perio。在基线以及第7、14和21天进行评估。通过微型计算机断层扫描评估牙槽骨丢失,并进行组织学炎症检查。DM小鼠血糖水平升高且存在胰岛素抵抗。与对照组和DM组相比,Perio组和DM-P组出现显著的骨丢失。形态计量分析显示,Perio组和DM-P组中存在大量炎性细胞且胶原纤维减少,尤其是在第7天。这种双鼠模型成功复制了DM和Perio的关键特征,维持了动物的整体健康,并且这些实验对象对两种干预程序的应激具有良好的耐受性。

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本文引用的文献

1
Chronic Inflammation and Glycemic Control: Exploring the Bidirectional Link Between Periodontitis and Diabetes.慢性炎症与血糖控制:探索牙周炎与糖尿病之间的双向联系
Dent J (Basel). 2025 Feb 26;13(3):100. doi: 10.3390/dj13030100.
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Diabetes, periodontal disease, and novel therapeutic approaches- host modulation therapy.糖尿病、牙周病与新型治疗方法——宿主调控疗法
Front Clin Diabetes Healthc. 2025 Mar 3;6:1529086. doi: 10.3389/fcdhc.2025.1529086. eCollection 2025.
3
Modulatory role of exogenous arachidonic acid in periodontitis with type 2 diabetes mellitus mice.
外源性花生四烯酸在2型糖尿病小鼠牙周炎中的调节作用
BMC Oral Health. 2025 Feb 19;25(1):264. doi: 10.1186/s12903-025-05525-1.
4
Bioactive Zn-V-Si-Ca Glass Nanoparticle Hydrogel Microneedles with Antimicrobial and Antioxidant Properties for Bone Regeneration in Diabetic Periodontitis.具有抗菌和抗氧化性能的生物活性锌-钒-硅-钙玻璃纳米颗粒水凝胶微针用于糖尿病性牙周炎的骨再生
ACS Nano. 2025 Mar 4;19(8):7981-7995. doi: 10.1021/acsnano.4c15227. Epub 2025 Feb 17.
5
Diabetes exacerbates periodontitis by disrupting IL-33-mediated interaction between periodontal ligament fibroblasts and macrophages.糖尿病通过破坏白细胞介素-33介导的牙周膜成纤维细胞与巨噬细胞之间的相互作用,加重牙周炎。
Int Immunopharmacol. 2025 Feb 6;147:113896. doi: 10.1016/j.intimp.2024.113896. Epub 2024 Dec 30.
6
Polyphenol-mediated redox-active hydrogel with HS gaseous-bioelectric coupling for periodontal bone healing in diabetes.多酚介导的具有 HS 气固生物电耦合的氧化还原活性水凝胶用于糖尿病牙周骨愈合。
Nat Commun. 2024 Oct 21;15(1):9071. doi: 10.1038/s41467-024-53290-6.
7
The high-fat diet and low-dose streptozotocin type-2 diabetes model induces hyperinsulinemia and insulin resistance in male but not female C57BL/6J mice.高脂肪饮食联合小剂量链脲佐菌素诱导的 2 型糖尿病模型可引起雄性而非雌性 C57BL/6J 小鼠高胰岛素血症和胰岛素抵抗。
Nutr Res. 2024 Nov;131:135-146. doi: 10.1016/j.nutres.2024.09.008. Epub 2024 Sep 14.
8
Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects.牙龈卟啉单胞菌的gingipain 通过直接的蛋白水解作用降解胰岛素受体,从而导致胰岛素抵抗。
Int J Oral Sci. 2024 Aug 1;16(1):53. doi: 10.1038/s41368-024-00313-z.
9
Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies.采用高脂饮食和低剂量链脲佐菌素治疗诱导的糖尿病大鼠表现出肠道微生物群失调和骨质疏松性骨病理。
Nutrients. 2024 Apr 19;16(8):1220. doi: 10.3390/nu16081220.
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Defining Porphyromonas gingivalis strains associated with periodontal disease.定义与牙周病相关的牙龈卟啉单胞菌菌株。
Sci Rep. 2024 Mar 14;14(1):6222. doi: 10.1038/s41598-024-56849-x.