Background The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury. Methods First, LCD nanoparticles, engineered with covalent conjugation between luminol and β-cyclodextrin (β-CD), were synthesized and examined. Then a mouse burn model was successfully established before the mouse body weight, intestinal histopathological manifestation, permeability, tight junction (TJ) expression and pro-inflammatory cytokines were determined in different groups. The proliferation, apoptosis, migration and reactive oxygen species (ROS) of intestinal epithelial cells (IECs) were assessed. Intraepithelial lymphocytes (IELs) were isolated and cultured for analysis by flow cytometry. Results LCD nanoparticle treatment significantly relieved the symptoms of burn-induced intestinal injury in the mouse model, including body weight loss and intestinal permeability abnormalities. Moreover, LCD nanoparticles remarkably recovered the mechanical barrier of the intestine after severe burn, renewed TJ structures, promoted IEC proliferation and migration, and inhibited IEC apoptosis. Mechanistically, LCD nanoparticles dramatically alleviated pro-inflammation factors (tumor necrosis factor-α, IL-17A) and ROS accumulation, which could be highly involved in intestinal barrier disruption. Furthermore, an increase in IL-17A and the proportion of IL-17A+Vγ4+ γδ T subtype cells was also observed in vitro in LPS-treated Vγ4+ γδ T cells, but the use of LCD nanoparticles suppressed this increase. Conclusions Taken together, these findings demonstrate that LCD nanoparticles have the protective ability to ameliorate intestinal barrier disruption and provide a therapeutic intervention for burn-induced intestinal injury.

中文翻译：

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鲁米诺缀合的环糊精生物纳米颗粒用于治疗严重烧伤引起的肠道屏障破坏。


背景严重烧伤后会发生肠道屏障完整性的破坏，并导致随后的炎症和氧化应激反应。由于传统方法的局限性，迫切需要一种新的肠道屏障保护策略。近年来，纳米粒子的应用已成为许多炎症相关疾病或氧化损伤的有前途的治疗方法之一。在此，我们开发了一种新型抗炎和抗氧化纳米颗粒，名为鲁米诺缀合环糊精（LCD），旨在评估其对严重烧伤引起的肠道损伤的保护作用。方法 首先，合成并检查了通过鲁米诺和 β-环糊精 (β-CD) 共价结合设计的 LCD 纳米颗粒。成功建立小鼠烧伤模型，测定各组小鼠体重、肠道组织病理学表现、通透性、紧密连接（TJ）表达和促炎细胞因子。评估肠上皮细胞（IEC）的增殖、凋亡、迁移和活性氧（ROS）。分离并培养上皮内淋巴细胞 (IEL)，用于流式细胞术分析。结果 LCD纳米颗粒治疗显着缓解了小鼠模型烧伤引起的肠道损伤的症状，包括体重减轻和肠道通透性异常。此外，LCD纳米粒子显着恢复了严重烧伤后肠道的机械屏障，更新了TJ结构，促进了IEC增殖和迁移，并抑制了IEC凋亡。 从机制上讲，LCD 纳米颗粒可显着减轻促炎症因子（肿瘤坏死因子-α、IL-17A）和 ROS 积累，这可能与肠道屏障破坏密切相关。此外，在体外LPS处理的Vγ4+γδT细胞中也观察到IL-17A和IL-17A+Vγ4+γδT亚型细胞比例的增加，但LCD纳米颗粒的使用抑制了这种增加。结论 综上所述，这些研究结果表明 LCD 纳米颗粒具有改善肠道屏障破坏的保护能力，并为烧伤引起的肠道损伤提供治疗干预。