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自交联透明质酸水凝胶作为治疗炎症性肠病的肠保护剂。

Self-crosslinking hyaluronic acid hydrogel as an enteroprotective agent for the treatment of inflammatory bowel disease.

机构信息

Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.

Liaoning Institute for Drug Control, No. 7 Chongshan West Road, Shenyang 110016, China.

出版信息

Int J Biol Macromol. 2024 Jul;273(Pt 2):132909. doi: 10.1016/j.ijbiomac.2024.132909. Epub 2024 Jun 6.

Abstract

The pathological changes in inflammatory bowel disease (IBD) include the disruption of intestinal barrier function and the infiltration of pathogenic microbes. The application of an artificial protective barrier at the site of inflammation can prevent bacterial infiltration, promote epithelial cell migration, and accelerate wound healing. In this study, dopamine-modified hyaluronic acid (HA-DA) was developed as a bioadhesive self-cross-linkable hydrogel, which acted as an enteroprotective agent to promote the healing of inflamed intestinal tissue. The adhesion strength HA-DA to mouse colon was 3.81-fold higher than HA. Moreover, HA-DA promoted Caco-2 cell proliferation and migration as well as had a strong physical barrier effect after gelation. After oral administration, the HA-DA reduced weight loss and attenuated impaired goblet cell function in mice with dextran sodium sulfate-induced IBD. In addition, HA-DA promoted restoration of the epithelial barrier by the upregulation of tight junction proteins. The results reported herein substantiated that self-cross-linkable hydrogel-based enteroprotective agents are a promising approach for the treatment of IBD.

摘要

炎症性肠病(IBD)的病理变化包括肠道屏障功能的破坏和致病微生物的浸润。在炎症部位应用人工保护屏障可以防止细菌渗透,促进上皮细胞迁移,并加速伤口愈合。在这项研究中,多巴胺修饰的透明质酸(HA-DA)被开发为一种具有生物黏附性的自交联水凝胶,作为肠保护剂促进发炎肠道组织的愈合。HA-DA 对小鼠结肠的黏附强度比 HA 高 3.81 倍。此外,HA-DA 在凝胶化后促进 Caco-2 细胞增殖和迁移,并具有很强的物理屏障作用。口服给药后,HA-DA 减轻了葡聚糖硫酸钠诱导的 IBD 小鼠的体重减轻和杯状细胞功能受损。此外,HA-DA 通过上调紧密连接蛋白促进上皮屏障的恢复。本研究结果证实,基于自交联水凝胶的肠保护剂是治疗 IBD 的一种有前途的方法。

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