国际口腔医学杂志 ›› 2026, Vol. 53 ›› Issue (2): 176-188.doi: 10.7518/gjkq.2026113

• 论著 • 上一篇    

低能量激光对高糖介导的巨噬细胞炎性衰老的作用研究

帕吾孜亚·阿布力孜(),邹浩南,董昊,崔爱民,孙乐章,王琪()   

  1. 口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心 四川大学华西口腔医院修复科 成都 610041
  • 收稿日期:2025-04-16 修回日期:2025-10-28 出版日期:2026-03-01 发布日期:2026-02-13
  • 通讯作者: 王琪
  • 作者简介:帕吾孜亚·阿布力孜,医师,硕士,Email:798546679@qq.com
  • 基金资助:
    国家自然科学基金(82470985);四川省自然科学基金(2024NSFSC0548)

Low-level laser therapy for hyperglycemia-associated inflammatory senescence in macrophages

Pawuziya Abulizi(),Haonan Zou,Hao Dong,Aimin Cui,Yuezhang Sun,Qi Wang()   

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Dept. of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2025-04-16 Revised:2025-10-28 Online:2026-03-01 Published:2026-02-13
  • Contact: Qi Wang
  • Supported by:
    National Natural Science Foundation of China(82470985);Natural Science Foundation of Sichuan Pro-vince(2024NSFSC0548)

摘要:

目的 高糖相关的巨噬细胞炎性衰老是诱导其功能障碍及牙周损伤的关键因素,本研究旨在探讨低能量激光治疗(LLLT)对该过程的调理作用。 方法 用不同能量密度的激光处理高糖转低糖环境培养的小鼠骨髓巨噬细胞(iBMDM),评估其吞噬、迁移功能及炎性衰老水平;构建糖尿病小鼠模型,比较单纯胰岛素治疗、单纯LLLT与胰岛素联合LLLT对牙周组织形态及炎性衰老表型的影响。 结果 LLLT增强iBMDM迁移及吞噬能力,并降低炎性衰老标志物的表达;体内实验中,LLLT联合胰岛素治疗改善糖尿病诱导的牙龈黏膜上皮增厚、层次紊乱、上皮钉突缩短及牙槽骨吸收,并减轻局部炎性衰老负荷。 结论 LLLT有效逆转高糖相关的巨噬细胞炎性衰老及其所致的牙周组织损伤,有望成为维护糖尿病患者口腔健康的有效辅助治疗方法。

关键词: 低能量激光, 巨噬细胞, 糖尿病, 炎性衰老

Abstract:

Objective Hyperglycemia-associated inflammatory senescence in macrophages is a key factor in inducing macrophage dysfunction and periodontal tissue damage. This study aims to explore the regulatory effects of low-level laser therapy (LLLT) on this process. Methods Bone marrow-derived macrophages (iBMDMs) cultured in a glucose-shift medium were subjected to laser treatments for evaluation in terms of phagocytosis, migration, and inflammatory senescence levels. Meanwhile, a diabetic mouse model was constructed to compare the effects of insulin monotherapy, LLLT monotherapy, and insulin-combined LLLT on the morphology and inflammatory senescence phenotype of periodontal tissues. Results LLLT enhanced cell migration and phagocytosis in iBMDMs, as well as reduced the expression of inflammatory senescence markers. In the in vivo experiments, LLLT combined with insulin treatment alleviated diabetes-induced gingival mucosal epithelial thickening, disordered stratification, shortened epithelial rete pegs, and alveolar bone resorption. Meanwhile, it reduced the inflammatory senescence burden. Conclusion LLLT effectively reverses hyperglycemia-associated sustained damage to macrophages and periodontal tissues. Thus, it shows strong potential as an effective adjuvant therapy for maintaining oral health in diabetic patients.

Key words: low-level laser therapy, macrophage, diabetes, inflammatory senescence

中图分类号: 

  • R616

图 1

Micro-CT 分析小鼠牙槽骨水平及骨体积分数A:各组小鼠下颌骨Micro-CT扫描后的三维重建图及X线图,黄色虚线区域为釉牙骨质界至牙槽嵴顶间面积,黄色箭头指牙槽间隔及根分叉处骨质吸收程度;B:牙槽间隔BV/TV统计分析;比例尺为1 mm。ns为P>0.05,*为P<0.05,***为P<0.01,****为P<0.001。"

图 2

牙龈组织HE染色小鼠上颌骨石蜡切片HE染色图。黄色线段为牙龈黏膜上皮厚度,单向箭头为上皮钉突,双向箭头为牙周膜间隙宽度;统计图为OlyVIA软件测量的牙龈黏膜上皮厚度及组间对比。比例尺:100 μm;ns为P>0.05,*为P<0.05,**为P<0.01,***为P<0.001。"

图 3

免疫染色检测牙周组织炎症衰老水平牙龈组织免疫染色,免疫荧光染色中蓝色荧光为细胞核,红色荧光为衰老因子p21,定位于细胞核;免疫组化染色中蓝色为细胞核,棕黄色为炎症因子IL-1β,定位于胞浆。p21、IL-1β抗体稀释比例均为1∶200;比例尺:100 μm。"

图 4

不同能量激光对细胞活力的影响A:活/死细胞染色表征3、6、18、30 J/cm2激光照射后24 h iBMDM细胞中活细胞(AM,绿色荧光)及死细胞(PI,红色荧光)数目;B:CCK-8试剂盒检测3、6、18、30 J/cm2激光照射后24、48 h对iBMDM细胞增殖活性的影响。比例尺:200 μm。ns为P>0.05,*为P<0.05。"

图 5

正常糖状态下激光对细胞迁移能力的影响A:划痕实验检测3、6、18和30 J/cm2激光照射L-929细胞14、24和48 h后划痕面积变化;B:Transwell实验检测3、6、18和30 J/cm2激光照射后迁移的iBMDM细胞数目变化(紫色为结晶紫染色的细胞),放大倍数:20倍;C:划痕实验14、24和28 h划痕面积及Transwell实验迁移细胞数目统计分析。**为P<0.01,****为P<0.001。"

图 6

Transwell检测巨噬细胞迁移能力放大倍数:20倍。**为P<0.05,***为P<0.01,****为P<0.001。"

图 7

红色荧光微球检测巨噬细胞吞噬能力蓝色为iBMDM细胞核、绿色为细胞骨架、红色为吞噬的荧光微球。"

图 8

SA-β-GAL衰老细胞染色A:橙色箭头所指的细胞为SA-β-Gal阳性RAW264.7细胞。B:SA-β-Gal阳性细胞定量统计结果。放大倍数:40倍。ns为P>0.05,*为P<0.05,***为P<0.01,****为P<0.001。"

图 9

WB检测巨噬细胞炎症衰老相关蛋白表达A:蛋白免疫印迹实验;B:蛋白相对表达量统计图。抗体稀释比例:p21(1∶2 000);p16(1∶1 000);IL-1β(1∶2 000)。*为P<0.05,***为P<0.01。"

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