负载盐酸米诺环素纳米二氧化硅微球在牙周炎炎症调控中的作用

doi:10.19439/j.sjos.2025.03.004

摘要/Abstract

摘要： 目的: 探讨负载盐酸米诺环素（minocycline hydrochloride,MH）的纳米二氧化硅微球（nano-silica microspheres,MSNion）对大鼠牙周炎炎症调控的效果。方法: 通过经典Stöber法制备介孔二氧化硅（mesoporous silica,MSN）,掺杂羟基磷灰石后得到MSNion。通过磁力搅拌将MH载入MSNion,利用电荷相互作用将具有抗炎抑菌作用的壳聚糖（chitosan,COS）吸附于其表面,形成MH@MSNion@COS微球,通过电镜、X射线衍射对微球进行表征。分为对照组（control）、MH组、MSNion@COS组和MH@MSNion@COS组。利用CCK-8细胞实验评估各组细胞毒性,ELISA试剂盒检测各组炎症因子（TNF-α、IL-6、IL-1β、iNOS、IL-10）的表达水平。在大鼠牙周炎模型中,按照细胞实验的分组进行处理,第0、1、2、4周时测量大鼠牙周探诊深度（probing depth,PD）及牙龈指数（gingival index,GI）,第4周时收集各组大鼠外周血,利用ELISA试剂盒检测血清中的炎症因子水平。结果: 制备得到粒径110 nm左右的纳米颗粒,电镜观察为规则球形。MH@MSNion@COS在第8天时降解为结构不清晰的碎片。体外药物释放测定显示,MH缓慢释放,释放率在第15天左右达到80%。细胞实验显示,MH@MSNion@COS组在50 μg/mL时,表现出最佳促细胞增殖活性（P<0.05）,细胞活性显著高于MH组、MSNion@COS组（P<0.05）,MH组与MSNion@COS组相比无显著差异。ELISA结果显示,第1天时,MH@MSNion@COS组各炎症因子表达显著低于LPS组（P<0.01）,但与MH组、MSNion@COS组相比无显著差异,第3天时,MH@MSNion@COS组M1型炎症因子表达较对照组减少,M2型炎症因子表达较对照组增加（P<0.05）。大鼠牙周炎各组给药后,MH@MSNion@COS组PD、GI显著下降,与其他各组相比差异显著（P<0.05）,炎症因子量显著低于其他各组（P<0.05）。结论: MH@MSNion@COS在体外及大鼠牙周炎模型中具有较好的炎症调控作用。

关键词: 介孔二氧化硅, 纳米材料, 牙周炎, 抗炎

Abstract: PURPOSE: To investigate the effect of minocycline hydrochloride(MH) loaded nano-silica microspheres(MSNion) on the inflammatory regulation of periodontitis in rats. METHODS: Mesoporous silica(MSN) was prepared by classical Stöber method and MSNion was obtained by doping hydroxyapatite. MH was loaded into MSNion by magnetic stirring, and chitosan (COS), which had anti-inflammatory and antibacterial effect, was adsorbed on its surface by using charge interactions, forming MH@MSNion@COS microspheres. The microspheres were characterized by electron microscopy and X-ray diffraction. The experiments were divided into control, MH, MSNion@COS and MH@MSNion@COS groups. The cytotoxicity of each group was assessed using the CCK-8 cell assay and the optimal concentration was determined. The expression levels of inflammatory factors(TNF-α, IL-6, IL-1β, iNOS, IL-10) were determined in each group using ELISA kits. In periodontitis model, the rats were treated according to the grouping of cell experiments, periodontal probing depth (PD) and gingival index (GI) of the rats were measured at 0, 1, 2, 4 weeks. At 4 weeks of the experiment, the peripheral blood of each group of rats was collected, and the levels of inflammatory factors in serum were detected by ELISA kits. RESULTS: Nanoparticles with a particle size of about 110 nm were prepared and observed as regular spheres by electron microscopy. MH@MSNion@COS degraded into fragments with unclear structure at the 8th day. In vitro drug release assay showed a slow release of MH, and the MH release rate reached 80% at about the 15th day. In cell experiment, MH@MSNion@COS showed the best cell proliferation activity at 50 μg/mL (P<0.05), and the cell activity was higher than that of MH group and MSNion@COS group(P<0.05). There was no significant difference between MH group and MSNion@COS group. ELISA results showed that the expression of inflammatory factors in MH@MSNion@COS group was significantly lower than that in LPS group at the first day(P<0.01), and there was no significant difference between MH group and MSNion@COS group. At the 3rd day, the expression of M1 inflammatory factors in MH@MSNion@COS group was lower than that in control group, and the expression of M2 inflammatory factors was higher than that in control group(P<0.05). PD and GI of MH@MSNion@COS group were significantly decreased after administration compared with other groups(P<0.05), and the amount of inflammatory factors was lower than other groups(P<0.05). CONCLUSIONS: MH@MSNion@COS has a good inflammatory regulation effect on experimental periodontitis in vitro and in vivo.

Key words: Mesoporous silica, Nanomaterials, Periodontitis, Anti-inflammatory effect

中图分类号:

R781.3

杨金鑫, 丁珂欣, 孙哲, 崔雅雯, 刘宗响. 负载盐酸米诺环素纳米二氧化硅微球在牙周炎炎症调控中的作用[J]. 上海口腔医学, 2025, 34(3): 244-250.

Yang Jinxin, Ding Kexin, Sun Zhe, Cui Yawen, Liu Zongxiang. Role of minocycline-loaded silica nanospheres in the regulation of periodontitis inflammation in rats[J]. Shanghai Journal of Stomatology, 2025, 34(3): 244-250.

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