中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (22): 3514-3520.doi: 10.12307/2022.279

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

一种新型免疫调节肽温敏凝胶治疗大鼠牙周炎

黄  杰，任  静，彭湃然，牟雁东   

  1. 四川省医学科学院·四川省人民医院，四川省成都市   610072
  • 收稿日期:2020-11-03 修回日期:2020-12-18 接受日期:2021-05-14 出版日期:2022-08-08 发布日期:2022-01-11
  • 通讯作者: 牟雁东，博士，主任医师，四川省医学科学院·四川省人民医院，四川省成都市 610072
  • 作者简介:黄杰，女，1993年生，四川省眉山市人，汉族，医师，主要从事口腔种植修复及牙周病学研究。
  • 基金资助:
    国家自然科学基金面上项目(82071168)，项目负责人：牟雁东；四川省青年科技创新研究团队项目(2016TD0008)，项目负责人：牟雁东

Treatment of periodontitis in rats with a novel temperature-sensitive gel with immunomodulatory peptide

Huang Jie, Ren Jing, Peng Pairan, Mu Yandong   

  1. Sichuan Academy of Medical Sciences · Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
  • Received:2020-11-03 Revised:2020-12-18 Accepted:2021-05-14 Online:2022-08-08 Published:2022-01-11
  • Contact: Mu Yandong, MD, Chief physician, Sichuan Academy of Medical Sciences · Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
  • About author:Huang Jie, Physician, Sichuan Academy of Medical Sciences · Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82071168 (to MYD); Sichuan Youth Science and Technology Innovation Research Team, No. 2016TD0008 (to MYD)

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摘要：

文题释义：
免疫调节肽：是一种结构稳定性高、对特定细胞器或细胞选择性小、毒性小的小分子多肽，包括抗菌肽、胸腺肽、成骨肽等，其中抗菌肽是带正电荷和少量疏水残基的阳离子两亲分子，具有广谱的抗菌活性，其原理为将先天免疫应答调节为免疫调节剂或与原核膜相互作用破坏膜功能，从而导致细胞杀伤，因而被认为是具有极好治疗潜力的新一代抗菌药物。
温敏凝胶：环境响应性水凝胶系统作为一种新型的给药系统，普遍用于缓释及控释等新型给药相关领域，温敏凝胶为其中一种在不同温度下呈现不同状态的凝胶体系。

背景：前期研究显示，免疫调节肽DP7具有良好的体外抗菌能力与免疫调节性。
目的：探究新型免疫调节肽DP7温敏凝胶对大鼠牙周炎的治疗效果。
方法：选取8周龄SD大鼠建立右上颌第一磨牙牙周炎模型，将建模成功的48只大鼠分为6组，自然愈合组不进行治疗，阳性对照组牙周袋内注入盐酸米诺环素，其余4组牙周袋内分别注入调节肽DP7浓度为0%(空白凝胶)，0.1%，0.3%，1%的温敏凝胶，每周注入1次，共4周。治疗4周后，检查各组牙周探诊深度、釉牙骨质界至牙槽嵴顶距离，并进行右上颌骨组织学与免疫组化染色。
结果与结论：①1%，0.3%DP7凝胶组大鼠牙周探诊深度、釉牙骨质界至牙槽嵴顶距离均低于阳性对照组(P < 0.05)；②苏木精-伊红染色显示，0.1%，0.3%，1%DP7凝胶组与阳性对照组牙龈组织较完整，上皮钉突恢复正常，成纤维细胞排列有序并可见新生的毛细血管，未观察到明显的破骨细胞，空白凝胶组及自然愈合组呈现牙周炎病理表现；③Masson染色显示，0.1%，0.3%，1%DP7凝胶组与阳性对照组可见大量新生的成纤维细胞有序排列，粗大的胶原增生并可见新生的毛细血管，1%及0.3%DP7凝胶组甚至可见类骨质或新骨形成，空白凝胶组与自然愈合组未见明显的胶原纤维增生及类骨质生成；④免疫组化染色显示，0.3%，1%DP7凝胶组肿瘤坏死因子α、白细胞介素1β表达量与阳性对照组比较无差异(P > 0.05)，白细胞介素10、骨形态发生蛋白2、成骨特异性转录因子2表达量均高于阳性对照组(P=0.000)；0.3%DP7凝胶组白细胞介素10、骨形态发生蛋白2、成骨特异性转录因子2表达量均高于1%DP7凝胶组(P < 0.05)；⑤结果表明，0.3%及1%免疫调节肽DP7凝胶对牙周炎具有良好的治疗作用，且0.3%免疫调节肽DP7凝胶的疗效最佳。

https://orcid.org/0000-0001-9976-2301 (黄杰) 

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: 材料, 免疫调节肽, 温敏凝胶, 缓释凝胶, 牙周炎

Abstract: BACKGROUND: Previous studies showed that immunomodulatory peptide DP7 has good antibacterial activity and immunomodulatory activity in vitro.  
OBJECTIVE: To investigate the therapeutic effect of a new type of immunoregulatory peptide DP7 temperature-sensitive gel on periodontitis in rats.
METHODS:  The periodontitis model of right maxillary first molar was established in 8-week-old SD rats, and the 48 successfully modeled rats were divided into 6 groups. Except for the natural healing group without treatment, minocycline hydrochloride was injected into periodontal pocket of positive control group. The periodontal pocket of the rest of the four groups were injected with regulatory peptide DP7 concentration 0% (blank gel), 0.1%, 0.3%, 1% temperature-sensitive gel, once a week for 4 weeks. Four weeks later, the periodontal probing depth and the distance between cementum enamel boundary and alveolar crest were examined; and histological and immunohistochemical staining of the right maxilla was performed.  
RESULTS AND CONCLUSION: (1) The probing depth and the distance between cementum enamel boundary and alveolar crest in 1% and 0.3% DP7 gel treatment groups were lower than those in positive control group (P < 0.05). (2) Hematoxylin-eosin staining showed that the gingival tissue of 0.1%, 0.3%, 1% DP7 gel groups and positive control group was more complete, and the epithelial pedicle process returned to normal, with the orderly array of fibroblasts and new capillaries, and no obvious osteoclasts were observed. The blank gel treatment group and the natural healing group showed the pathological manifestations of periodontitis. (3) Masson staining showed that a large number of new fibroblasts were orderly arranged in the 0.1%, 0.3%, and 1% DP7 gel groups and the positive control group, and bulging collagen hyperplasia and new capillaries were visible. Osteoid or new bone formation was even observed in the 1% and 0.3% DP7 gel groups. However, the blank gel group and the natural healing group had no obvious collagen fiber proliferation and osteoid formation. (4) Immunohistochemical staining showed that the expression levels of tumor necrosis factor-α and interleukin-1β in 0.3% and 1% DP7 gel groups were not significantly different from those in the positive control group (P > 0.05). The expression levels of interleukin-10, bone morphogenetic protein-2 and osteoblast specific transcription factor 2 in 0.3% and 1% DP7 gel groups were higher than those in the positive control group (P=0.000). The expression levels of interleukin-10, bone morphogenetic protein-2 and osteoblast specific transcription factor 2 in 0.3% DP7 gel group were higher than those in the 1% DP7 gel group (P < 0.05). (5) The results showed that 0.3% and 1% immunoregulatory peptide DP7 gel had favorable therapeutic effect on periodontitis, and 0.3% immunoregulatory peptide DP7 gel had the best therapeutic effect.

Key words: material, immunomodulatory peptide, temperature sensitive gel, delayed release gel, periodontitis

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