| 15 | 0 | 23 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探究羟基酪醇介导巨噬细胞极化对烧伤大鼠创面愈合的影响及其机制。方法 SD大鼠随机分为烧伤组、羟基酪醇组、羟基酪醇+ov-NC组和羟基酪醇+ov-S100A9组，每组10只。采用金属砝码烧伤法建立烧伤模型。计算创面愈合率；HE染色观察大鼠创面皮肤组织病理形态变化；免疫荧光检测大鼠创面皮肤组织M1和M2型巨噬细胞比例；ELISA检测大鼠创面皮肤组织巨噬细胞炎症因子水平；Western blot检测大鼠创面皮肤组织S100A9/TLR4/NF-κB信号通路表达。结果 与烧伤组相比，羟基酪醇组和羟基酪醇+ov-NC组大鼠创面愈合能力增加且病理损伤改善，M1型巨噬细胞及相关因子减少，M2型巨噬细胞及相关因子增加，S100A9、TLR4和p-NF-κB p65蛋白表达下调；与羟基酪醇组和羟基酪醇+ov-NC组相比，羟基酪醇+ov-S100A9组大鼠创面愈合能力降低且病理损伤加重，M1型巨噬细胞及相关因子增加，M2型巨噬细胞及相关因子减少，S100A9、TLR4和p-NF-κB p65蛋白表达上调。结论 羟基酪醇通过下调S100A9促进烧伤大鼠创面愈合，其机制可能与抑制TLR4/NF-κB信号通路激活改善M1/M2型巨噬细胞失衡有关。
Abstract：Objective To explore the effects of hydroxytyrosol-mediated macrophage polarization on burn wound healing in rats. Methods SD rats were randomly divided into burn group, hydroxytyrosol group, hydroxytyrosol + ovNC group and hydroxytyrosol +ov-S100A9 group, with 10 rats in each group. Burn model was established by metal weight burn method. Wound healing rate was calculated; HE staining was used to observe the pathological changes of wound skin tissue in rats; immunofluorescence was used to detect the ratios of M1 and M2 macrophages in the wound skin of rats;ELISA was used to detect the levels of macrophage inflammatory factors in the wound skin of rats; Western blot was used to detect the expression of S100A9/TLR4/NF-κB signal pathway in wound skin of rats. Results Compared with the burn group, hydroxytyrosol group and hydroxytyrosol+ov-NC group demonstrated higher wound healing ability and alleviated pathological damage, lower levels of M1 type macrophages and related factors, higher levels of M2 type macrophages and related factors, and lower expression of S100A9, TLR4 and p-NF-κB p65 proteins. Compared with hydroxytyrosol group and hydroxytyrosol +ov-NC group, S100A9 overexpression reduced the wound healing ability and aggravated the pathological damage, increased M1 type macrophages and related factors, decreased M2 type macrophages and related factors, and increased the expression of S100A9, TLR4 and p-NF-κB p65 proteins in hydroxytyrosol+ov-S100A9 group.Conclusion Hydroxytyrosol promotes wound healing in burn rats by down-regulating S100A9, and its mechanism may be related to inhibiting the activation of TLR4/NF-κB signaling pathway and improving the imbalance of M1/M2 macrophages.
[1] Parry I, Bell J. Associations between burn care services and impairment at discharge after burn injury:Analysis of the Global Burn Registry[J]. Burns, 2024, 50(4):813-822.
[2] Fuchs C, Pham L, Wang Y, et al. MagneTEskin-Reconstructing skin by magnetically induced assembly of autologous microtissue cores[J]. Sci Adv, 2021, 7(41):eabj0864.
[3] Chen L, Li Z, Zheng Y, et al. 3D-printed dermis-specific extracellular matrix mitigates scar contraction via inducing early angiogenesis and macrophage M2 polarization[J].Bioact Mater, 2022, 10(3):236-246.
[4] Kim H, Wang SY, Kwak G, et al. Exosome-guided phenotypic switch of M1 to M2 macrophages for cutaneous wound healing[J]. Adv Sci(Weinh), 2019, 6(20):1900513.
[5]徐明芝,安娜,白亚飞,等. miR-532-3p靶向抑制Notch1信号通路对慢性肾脏病大鼠巨噬细胞极化的影响[J].中国免疫学杂志, 2025, 41(2):310-314.
[6] Cui Z, Li Y, Qin Y, et al. Polymyxin B-targeted liposomal photosensitizer cures MDR A. baumannii burn infections and accelerates wound healing via M(1)/M(2)macrophage polarization[J]. J Control Release, 2024, 366(1):297-311.
[7] Utami ND, Nordin A, Katas H, et al. Molecular action of hydroxytyrosol in wound healing:An in vitro evidencebased review[J]. Biomolecules, 2020, 10(10):1397.
[8] de Carvalho Faria RV, Duarte MS, de Souza Nogueira J, et al. Nrf2 activation by hydroxytyrosol and dimethyl fumarate ameliorates skin tissue repair in high-fat diet-fed mice by promoting M2 macrophage polarization and normalizing inflammatory response and oxidative damage[J]. J Biochem Mol Toxicol, 2024, 38(2):e23652.
[9]潘配强,于芬芬,单文红,等.羟基酪醇对对比剂诱导的肾损伤的保护作用[J].临床肾脏病杂志, 2019, 19(12):917-921.
[10] Duarte MS, Fuhro VM, de Souza Nogueira J, et al. Polyphenol hydroxytyrosol present olive oil improves skin wound healing of diabetic mice[J]. Wound Repair Regen, 2024, 32(6):904-915.
[11] Zhang K, Guo J, Yan W, et al. Macrophage polarization in inflammatory bowel disease[J]. Cell Commun Signal, 2023,21(1):367.
[12] Rodriguez-Morales P, Franklin RA. Macrophage phenotypes and functions:resolving inflammation and restoring homeostasis[J]. Trends Immunol, 2023, 44(12):986-998.
[13]冯莹,张妍,雷杰,等.巨噬细胞极化对血管平滑肌细胞PI3K/Akt/mTOR信号通路的影响[J].中国免疫学杂志, 2025, 41(2):315-319.
[14] Chen C, Liu T, Tang Y, et al. Epigenetic regulation of macrophage polarization in wound healing[J]. Burns Trauma, 2023, 11(3):tkac057.
[15] Boucher J, Gilbert C, Bose S, et al. S100A9:The unusual suspect connecting viral infection and inflammation[J]. J Immunol, 2024, 212(10):1523-1529.
[16] Najarro KM, Boe DM, Walrath TM, et al. Advanced age exacerbates intestinal epithelial permeability after burn injury in mice[J]. Exp Gerontol, 2022, 158(2):111654.
[17] Franz S, Ertel A, Engel KM, et al. Overexpression of S100A9 in obesity impairs macrophage differentiation via TLR4-NFkB-signaling worsening inflammation and wound healing[J]. Theranostics, 2022, 12(4):1659-1682.
[18] Leri M, Sun D, Svedruzic ZM, et al. Pro-inflammatory protein S100A9 targeted by a natural molecule to prevent neurodegeneration onset[J]. Int J Biol Macromol, 2024, 276(Pt 2):133838.
基本信息:
DOI：10.13431/j.cnki.immunol.j.20250012
中图分类号:R644
引用信息:
[1]陈福泰,刘永硕,陈远征.羟基酪醇介导S100A9/TLR4/NF-κB信号通路调节巨噬细胞极化改善烧伤大鼠创面愈合[J].免疫学杂志,2025,41(02):86-90+96.DOI:10.13431/j.cnki.immunol.j.20250012.
基金信息: