枸杞糖肽喷雾防治烟草诱导的口腔黏膜损伤相关研究

doi:10.13591/j.cnki.kqyx.2026.02.003

摘要/Abstract

摘要：

目的开发一种基于氧化海藻酸钠(oxidized sodium alginate,OSA)和明胶微球的枸杞糖肽(lycium barbarum glycopeptide,LbGP)喷雾制剂,用于缓解烟草燃烧产物引起的口腔黏膜炎。方法 ①制备烟草提取物(cigarette smoke extraction,CSE),通过CCK-8法筛选适宜浓度CSE作为作用浓度。②制备负载LbGP的明胶微球和喷雾基质OSA,检测其形貌、氧化度及理化性质。③测试LbGP-OSA喷雾的pH值、缓释性、稳定性和黏附性。④通过CCK-8法、活/死细胞染色、划痕实验、ROS及GSH检测,评估喷雾对烟草损伤的人牙龈成纤维细胞(human gingival fibroblasts,HGFs)的保护及抗氧化作用。⑤构建吸烟大鼠口腔黏膜炎模型,通过溃疡愈合、HE染色、Masson染色及免疫组化分析喷雾的促愈合效果。结果 ①LbGP-OSA喷雾氧化度29.17%±2.46%,微球粒径(13.3±2.3)μm,pH=6.8,缓释性及黏附性良好;②喷雾显著提升HGFs存活率及迁移能力,降低ROS并提高GSH水平;③喷雾组大鼠黏膜炎愈合更快,给药9 d后上皮恢复完整,TNF-α、IL-6表达降低(P<0.05),IL-10升高(P<0.05),且无毒性。结论 LbGP-OSA喷雾具备缓释性、黏附性和生物相容性,可减轻烟草对口腔黏膜的氧化损伤,调控炎症因子表达,促进愈合且安全性良好,具有临床应用潜力。

关键词: 枸杞糖肽, 喷雾剂, 烟草, 口腔, 人牙龈成纤维细胞

Abstract:

Objective To develop a lycium barbarum glycopeptide(LbGP) spray based on oxidized sodium alginate(OSA) and gelatin microspheres to alleviate tobacco combustion product-induced oral mucositis. Methods ①Cigarette smoke extract(CSE) was prepared and screened for the optimal intervention concentration through CCK-8 assay. ②LbGP-loaded gelatin microspheres and OSA matrix were fabricated, characterizing morphology, oxidation degree, and physicochemical properties. ③pH, sustained-release capability, stability, and adhesion of LbGP-OSA spray were evaluated. ④The protective and antioxidant effects of the spray on tobacco-damaged human gingival fibroblasts(HGFs)were assessed by CCK-8 assay, live/dead staining, scratch assay, ROS, and GSH detection. ⑤A smoking rat oral mucositis model was established to analyze the healing efficacy through ulcer recovery, HE/Masson staining, and immunohistochemistry. Results ①LbGP-OSA spray exhibited an oxidation degree of 29.17%±2.46%, with microsphere size (13.3±2.3)μm, pH=6.8, and favorable sustained-release/adhesion properties. ②The spray significantly improved HGFs viability and migration, reduced ROS levels, and elevated GSH content. ③In rats, the spray accelerated mucositis healing(epithelial integrity restored at day 9), down-regulated TNF-α and IL-6(P<0.05), up-regulated IL-10(P<0.05), and showed no toxicity. Conclusion The LbGP-OSA spray demonstrates sustained-release capability, adhesion, and biocompatibility, mitigates oxidative damage, modulates inflammatory cytokines, promotes mucosal healing, and holds clinical potential for tobacco-related oral injuries.

Key words: lycium barbarum glycopeptide, spray, tobacco, oral, human gingival fibroblasts

中图分类号:

R781.5

倪亦婷, 肖逊, 李东亮, 张艇, 李品鹤, 袁伦, 王跃, 牟雁东. 枸杞糖肽喷雾防治烟草诱导的口腔黏膜损伤相关研究[J]. 口腔医学, 2026, 46(2): 97-105.

NI Yiting, XIAO Xun, LI Dongliang, ZHANG Ting, LI Pinhe, YUAN Lun, WANG Yue, MU Yandong. Study on the prevention and treatment of tobacco-induced oral mucosa damage by lycium barbarum glycopeptide[J]. Stomatology, 2026, 46(2): 97-105.

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参考文献 21

[1]	Lai S, Liu C, Liu C, et al. Lycium barbarum polysaccharide-glycoprotein promotes osteogenesis in hPDLSCs ERK activation[J]. Oral Dis, 2023, 29(8): 3503-3513. doi: 10.1111/odi.v29.8
[2]	Boškov IA, Savić IM, Grozdanić Stanisavljević ND, et al. Stabilization of black locust flower extract via encapsulation using alginate and alginate-chitosan microparticles[J]. Polymers(Basel), 2024, 16(5): 688.
[3]	Yang L, Gu TW, Xu Y, et al. Plant polysaccharides as novel biomaterials for microcapsule construction and therapeutics delivery[J]. Int J Pharm, 2022, 625: 122137. doi: 10.1016/j.ijpharm.2022.122137
[4]	Lun Y, Li XY, Ge LM, et al. Emulsion template method for the fabrication of gelatin-based scaffold with a controllable pore structure[J]. ACS Applied Materials & Interfaces, 2019, 11(1):269-277.
[5]	He SQ, Wen N, Chen X, et al. Emulsion template fabricated heterogeneous bilayer gelatin-based scaffolds with sustained-delivery of lycium barbarum glycopeptide for periodontitis treatment[J]. J Biomater Sci Polym Ed, 2024, 35(9): 1379-1399. doi: 10.1080/09205063.2024.2329455
[6]	Changsan N, Srichana T, Atipairin A, et al. Wound healing efficacy of a polymeric spray film solution containing centellaasiatica leaf extract on acute wounds[J]. J Wound Care, 2023, 32(Sup12): S22-S32. doi: 10.12968/jowc.2023.32.Sup12.S22 pmid: 38063299
[7]	Zhao X, Wang KL, Dou NX, et al. Oil body extraction from high-fat and high-protein soybeans by laccase cross-linked beet pectin: Physicochemical and oxidation properties[J]. J Sci Food Agric, 2023, 103(7): 3550-3557. doi: 10.1002/jsfa.v103.7
[8]	Murata K, Fujita N, Takahashi R. Ninjinyoeito ameliorated cigarette smoke extract-induced apoptosis and inflammation through JNK signaling inhibition in human lung fibroblasts[J]. BMC Complement Med Ther, 2022, 22(1): 96. doi: 10.1186/s12906-022-03574-5 pmid: 35361188
[9]	Hardin LT, Abid N, Vang D, et al. miRNAs mediate the impact of smoking on dental pulp stem cells via the p53 pathway[J]. Toxicol Sci, 2024, 200(1): 47-56. doi: 10.1093/toxsci/kfae042
[10]	Hardin LT, Vang D, Thor D, et al. Cigarette smoking exposure disrupts the regenerative potential of dental pulp stem cells[J]. Tob Induc Dis, 2023, 21: 101. doi: 10.18332/tid/168125 pmid: 37533959
[11]	吴芸菲, 张黎, 张旭凤, 等. 烟草提取物对牙周炎小鼠牙周组织TLR4炎症通路的影响[J]. 口腔医学研究, 2019, 35(7): 651-656. doi: 10.13701/j.cnki.kqyxyj.2019.07.009
[12]	吴琳. 烟草提取物对牙周炎小鼠Th17/Treg细胞免疫平衡及相关转录因子表达的影响[J]. 中国免疫学杂志, 2019, 35(18): 2200-2205.
[13]	Boehm O, Zur B, Koch A, et al. Clinical chemistry reference database for Wistar rats and C57/BL6 mice[J]. Biol Chem, 2007, 388(5):547-554. pmid: 17516851
[14]	Peng Q, Duan N, Wang X, et al. The potential roles of cigarette smoke-induced extracellular vesicles in oral leukoplakia[J]. Eur J Med Res, 2023, 28(1): 250. doi: 10.1186/s40001-023-01217-0 pmid: 37481562
[15]	Hou RX, Yang JT, Li XX, et al. Decoding different oxidative stress pathways in periodontitis: A comparative review of mechanisms of traditional tobacco smoke and electronic smoke aerosol[J]. Arch Toxicol, 2025, 99(6):2261-2276. doi: 10.1007/s00204-025-04011-5
[16]	Marinucci L, Coniglio M, Valenti C, et al. In vitro effects of alternative smoking devices on oral cells: Electronic cigarette and heated tobacco product versus tobacco smoke[J]. Arch Oral Biol, 2022, 144: 105550. doi: 10.1016/j.archoralbio.2022.105550
[17]	Bozkurt SB, Nielsen FH, Hakki SS. Boric acid reverses nicotine-induced cytokine expressions of human gingival fibroblasts[J]. Biol Trace Elem Res, 2023, 201(3): 1174-1180. doi: 10.1007/s12011-022-03243-1
[18]	Zhu S, Li X, Dang BR, et al. Lycium barbarum polysaccharide protects HaCaT cells from PM_2.5-induced apoptosis inhibiting oxidative stress, ER stress and autophagy[J]. Redox Rep, 2022, 27(1): 32-44. doi: 10.1080/13510002.2022.2036507
[19]	Wang SW, Song XM, Wei LY, et al. Role of mitophagy in cigarette smoke-induced lung epithelial cell injury in vitro[J]. Curr Mol Med, 2023, 23(10): 1130-1140.
[20]	Cyprus GN, Overlin JW, Hotchkiss KM, et al. Cigarette smoke increases pro-inflammatory markers and inhibits osteogenic differentiation in experimental exposure model[J]. Acta Biomater, 2018, 76: 308-318. doi: S1742-7061(18)30361-1 pmid: 29902595
[21]	Golshani S, Vatanara A, Balalaie S, et al. Development of a novel histatin-5 mucoadhesive gel for the treatment of oral mucositis:Characterization and evaluation[J]. AAPS Pharm Sci Tech, 2023, 24(7): 177. doi: 10.1208/s12249-023-02632-6