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生物活性玻璃在治疗溃疡性结肠炎中对Toll样受体4/髓样分化因子88/核因子κB信号通路的调控作用

Bioactive glass in the treatment of ulcerative colitis to regulate the TLR4 / MyD88 / NF-κB pathway.

作者信息

Wang Wenhao, Jia Shengyuan, Miao Guohou, Sun Zhenmin, Yu Feng, Gao Zhixing, Li Yuli

机构信息

Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao Municipal Hospital, Qingdao 266071, China; Weifang Medical University, Weifang 261042, China.

Weifang Medical University, Weifang 261042, China.

出版信息

Biomater Adv. 2023 Sep;152:213520. doi: 10.1016/j.bioadv.2023.213520. Epub 2023 Jun 14.

Abstract

Ulcerative colitis (UC) is a chronic and recurrent intestinal disease of unknown aetiology, and the few treatments approved for UC have serious side effects. In this study, a new type of uniformly monodispersed calcium-enhanced radial mesoporous micro-nano bioactive glass (HCa-MBG) was prepared for UC treatment. We established cellular and rat UC models to explore the effects and mechanism of HCa-MBG and traditional BGs (45S5, 58S) on UC. The results showed that BGs significantly reduced the cellular expression of several inflammatory factors, such as IL-1β, IL-6, TNF-α and NO. In the animal experiments, BGs were shown to repair the DSS-damaged colonic mucosa. Moreover, BGs downregulated the mRNA levels of the inflammatory factors IL-1β, IL-6, TNF-α and iNOS, which were stimulated by DSS. BGs were also found to manage the expression of key proteins in NF-kB signal pathway. However, HCa-MBG was more effective than traditional BGs in terms of improving UC clinical manifestations and reducing the expression of inflammatory factors in rats. This study confirmed for the first time that BGs can be used as an adjuvant drug in UC treatment, thereby preventing UC progression.

摘要

溃疡性结肠炎(UC)是一种病因不明的慢性复发性肠道疾病,目前获批用于治疗UC的少数药物具有严重的副作用。在本研究中,制备了一种新型的单分散钙增强径向介孔微纳生物活性玻璃(HCa-MBG)用于治疗UC。我们建立了细胞和大鼠UC模型,以探究HCa-MBG和传统生物活性玻璃(45S5、58S)对UC的影响及作用机制。结果表明,生物活性玻璃显著降低了几种炎症因子的细胞表达,如白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和一氧化氮(NO)。在动物实验中,生物活性玻璃显示出可修复由葡聚糖硫酸钠(DSS)损伤的结肠黏膜。此外,生物活性玻璃下调了由DSS刺激产生的炎症因子IL-1β、IL-6、TNF-α和诱导型一氧化氮合酶(iNOS)的mRNA水平。还发现生物活性玻璃可调控核因子-κB(NF-κB)信号通路中关键蛋白的表达。然而,在改善UC临床表现和降低大鼠炎症因子表达方面,HCa-MBG比传统生物活性玻璃更有效。本研究首次证实生物活性玻璃可作为UC治疗的辅助药物,从而防止UC病情进展。

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