中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (17): 2690-2695.doi: 10.12307/2024.448

• 组织工程口腔材料 tissue-engineered oral materials • 上一篇    下一篇

人β-防御素3水凝胶治疗大鼠牙周炎

王玉雪1,周  歆1,郑钧元2,周永庆2   

  1. 1湖北医药学院,湖北省十堰市  442000;2十堰市人民医院(湖北医药学院附属人民医院)口腔科,湖北省十堰市  442000
  • 收稿日期:2023-06-12 接受日期:2023-08-01 出版日期:2024-06-18 发布日期:2023-12-15
  • 通讯作者: 周永庆,主任医师,副教授,十堰市人民医院(湖北医药学院附属人民医院)口腔科,湖北省十堰市 442000
  • 作者简介:王玉雪,女,1997年生,云南省昆明市人,汉族,在读硕士,医师,主要从事牙体牙髓及牙周病学研究。
  • 基金资助:
    湖北省卫生健康科研基金资助(WJ2019F045),项目负责人:郑钧元

Human beta-defensin 3 hydrogel for treatment of periodontitis in rats

Wang Yuxue1, Zhou Xin1, Zheng Junyuan2, Zhou Yongqing2   

  1. 1Hubei University of Medicine, Shiyan 442000, Hubei Province, China; 2Department of Stomatology, Shiyan Renmin Hospital (Affiliated Renmin Hospital of Hubei University of Medicine), Shiyan 442000, Hubei Province, China
  • Received:2023-06-12 Accepted:2023-08-01 Online:2024-06-18 Published:2023-12-15
  • Contact: Zhou Yongqing, Chief physician, Associate professor, Department of Stomatology, Shiyan Renmin Hospital (Affiliated Renmin Hospital of Hubei University of Medicine), Shiyan 442000, Hubei Province, China
  • About author:Wang Yuxue, Master candidate, Physician, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
  • Supported by:
    Scientific Research Project of Health Commission of Hubei Province, No. WJ2019F045 (to ZJY)

摘要:


文题释义:

水凝胶:一种新型给药系统,此次研究采用的是温敏型水凝胶,其在室温下呈液态,37 ℃下在一定时间内呈现凝胶状,它能与牙周袋内不规则形状很好地贴合,长时间黏附于牙周袋内壁并稳定释放药物。
牙周炎:是仅次于癌症、心脑血管疾病的威胁人类健康的第三大疾病,是牙周支持组织发生持续性、不可逆性的损伤,正在逐渐成为成人牙齿脱落的第一大病因。


背景:既往研究显示人β-防御素3具有显著的抗真菌、抗细菌和抗病毒活性,并且在连接先天和获得性免疫应答中起到重要的桥梁作用。

目的:观察人β-防御素3水凝胶治疗大鼠牙周炎的效果。
方法:以泊洛沙姆188与407为基质,采用冷溶法构建空白水凝胶,将人β-防御素3与该水凝胶混合制备人β-防御素3水凝胶。将25只SD大鼠随机分为5组,每组5只:健康组不做任何处理,牙周炎组、空白水凝胶组、盐酸米诺环素组、载药水凝胶组采用正畸结扎钢丝法构建牙周炎模型,造模8周后于颊侧与腭侧牙周袋内分别注射空白水凝胶、盐酸米诺环素、人β-防御素3水凝胶,1次/周,连续给药4周后进行相关检测。

结果与结论:①与健康组比较,牙周炎组大鼠牙周菌斑指数、牙龈出血指数及牙周探诊深度均增加(P < 0.01);与牙周炎组比较,盐酸米诺环素组与载药水凝胶组大鼠牙周菌斑指数、牙龈出血指数及牙周探诊深度均减少(P < 0.05);②大鼠脏器苏木精-伊红染色显示载药水凝胶无毒性作用;③体视显微镜与Micro CT扫描显示,与健康组比较,牙周炎组大鼠牙根暴露及釉牙骨质界-牙槽嵴顶距离均增加(P < 0.05);与牙周炎组比较,盐酸米诺环素组与载药水凝胶组大鼠牙根暴露、釉牙骨质界-牙槽嵴顶距离均减少(P < 0.05);④苏木精-伊红、Masson及抗酒石酸酸性磷酸酶染色显示,牙周炎组、空白水凝胶组大鼠牙周炎症明显、纤维结构混乱、破骨细胞活跃,盐酸米诺环素组、载药水凝胶组大鼠牙周炎症水平降低、纤维排列较规则、破骨细胞减少;⑤qRT-PCR检测显示,与健康组比较,牙周炎组大鼠牙龈组织中白细胞介素1β、肿瘤坏死因子α、白细胞介素6、诱导型一氧化氮合酶的mRNA表达升高(P < 0.05);与牙周炎组比较,盐酸米诺环素组、载药水凝胶组大鼠牙龈组织中白细胞介素1β、肿瘤坏死因子α、白细胞介素6、诱导型一氧化氮合酶的mRNA表达降低(P < 0.05);⑥结果表明,人β-防御素3水凝胶可通过降低炎症因子的相对表达及抑制破骨来减轻大鼠牙周组织炎症。

https://orcid.org/0009-0002-7776-4204(王玉雪)

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料口腔生物材料纳米材料缓释材料材料相容性组织工程

关键词: 人β-防御素3, 水凝胶, 温敏型, 牙周炎, 炎症因子

Abstract: BACKGROUND: Previous studies have shown that human beta-defensin 3 has significant antifungal, antibacterial, and antiviral activities and plays an important bridging role in linking innate and acquired immune responses. 
OBJECTIVE: To observe the effect of human beta-defensin 3 hydrogel on treatment of periodontitis in rats.
METHODS: Using Poloxamer 188 and 407 as the matrix, a blank hydrogel was constructed by cold solution. Human beta-defensin 3 hydrogel was prepared by mixing human beta-defensin 3 with the hydrogel. Twenty-five SD rats were randomly divided into five groups with five rats in each group: No treatment was given in the healthy group. The periodontitis model was constructed by the orthodontic ligature wire method in the periodontitis group, blank hydrogel group, minocycline hydrochloride group, and human beta-defensin 3 hydrogel group. 8 weeks after modeling, blank hydrogel, minocycline hydrochloride, and human β-defensin 3 hydrogel were injected into the buccal and palatal periodontal bags, once a week, and relevant tests were carried out after continuous administration for 4 weeks.
RESULTS AND CONCLUSION: (1) Compared with the healthy group, periodontal plaque index, gingival bleeding index, and periodontal probing depth were increased in the periodontitis group (P < 0.01). Compared with the periodontitis group, the periodontal plaque index, gingival bleeding index, and periodontal probing depth of rats were decreased in the minocycline hydrochloride group and the human beta-defensin 3 hydrogel group (P < 0.05). (2) Hematoxylin-eosin staining proved that the hydrogel was not toxic to the rat organism. (3) Stereomicroscopy and Micro CT showed that compared with the healthy group, the root exposure and the distance between enamel cementum boundary and alveolar crest of the periodontitis group were increased (P < 0.05). Compared with the periodontitis group, the root exposure and the distance between enamel cementum boundary and alveolar crest of rats were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group (P < 0.05). (4) Hematoxylin-eosin, Masson, and tartrate-resistant acid phosphatase staining showed that periodontal inflammation was obvious, fiber structure was disordered and osteoclasts were active in the periodontitis group and blank hydrogel group, while periodontal inflammation was decreased, fiber arrangement was more regular, and osteoclasts were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group. (5) qRT-PCR showed that compared with the healthy group, the mRNA expressions of interleukin 1β, tumor necrosis factor α, interleukin 6, and inducible nitric oxide synthase were increased in the periodontitis group (P < 0.05). Compared with the periodontitis group, the mRNA expressions of interleukin 1β, tumor necrosis factor α, interleukin 6, and inducible nitric oxide synthase in gingival tissue of rats were decreased in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group (P < 0.05). (6) The results showed that human beta-defensin 3 hydrogel was able to attenuate inflammation in rat periodontal tissues by decreasing the relative expression of inflammatory factors and inhibiting osteoblasts. 

Key words: human beta-defensin 3, hydrogel, temperature sensitive type, periodontitis, inflammatory factor

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