School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing 100081, China.
Int J Mol Sci. 2021 Mar 8;22(5):2722. doi: 10.3390/ijms22052722.
Dragon's Blood is a red resin from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has shown protective effects on intestinal disorders. Microgravity could alter intestinal homeostasis. However, the potential herbal drugs for preventing intestine epithelial barrier (IEB) dysfunction under microgravity are not available. This study aimed to investigate the effects of Dragon's Blood (DB) on microgravity-induced IEB injury and explore its underlying mechanism. A rat tail-suspension model was used to simulate microgravity (SMG). Histomorphology, ultrastructure, permeability, and expression of junction proteins in jejunum, ileum, and colon of SMG rats were determined. Proteomic analysis was used to identify differentially expressed proteins (DEPs) in rat ileum mucosa altered by DB. The potential mechanism of DB to protect IEB dysfunction was validated by western blotting. The effects of several components in DB were evaluated in SMG-treated Caco-2 cells. DB protected against IEB disruption by repairing microvilli and crypts, inhibiting inflammatory factors, lowering the permeability and upregulating the expression of tight and adherens junction proteins in the ileum of SMG rats. Proteomic analysis showed that DB regulated 1080 DEPs in rat ileum mucosa. DEPs were significantly annotated in cell-cell adhesion, focal adhesion, and cytoskeleton regulation. DB increased the expression of Rac1-WAVE2-Arp2/3 pathway proteins and F-actin to G-actin ratio, which promoted the formation of focal adhesions. Loureirin C in DB showed a protective effect on epithelial barrier injury in SMG-treated Caco-2 cells. DB could protect against IEB dysfunction induced by SMG, and its mechanism is associated with the formation of focal adhesions mediated by the Rac1-WAVE2-Arp2/3 pathway, which benefits intestinal epithelial cell migration and barrier repair.
血竭是从龙舌兰科龙舌兰（中国云南）中提取的红色树脂。作为一种传统的中药，它对肠道紊乱有保护作用。微重力会改变肠道内环境的平衡。然而，用于预防微重力下肠道上皮屏障（IEB）功能障碍的潜在草药药物尚不可用。本研究旨在探讨血竭（DB）对模拟微重力（SMG）诱导的 IEB 损伤的影响及其潜在机制。采用大鼠尾部悬吊模型模拟微重力（SMG）。测定 SMG 大鼠空肠、回肠和结肠的组织形态、超微结构、通透性和连接蛋白的表达。采用蛋白质组学分析鉴定 DB 改变的大鼠回肠黏膜中差异表达蛋白（DEPs）。采用 Western blot 验证 DB 保护 IEB 功能障碍的潜在机制。评价了 DB 中几种成分在 SMG 处理的 Caco-2 细胞中的作用。DB 通过修复微绒毛和隐窝、抑制炎症因子、降低通透性和上调 SMG 大鼠回肠紧密连接和黏附连接蛋白的表达来保护 IEB 免受破坏。蛋白质组学分析显示，DB 调节了大鼠回肠黏膜中的 1080 个 DEPs。DEPs 在细胞-细胞黏附、焦点黏附和细胞骨架调节中显著注释。DB 增加 Rac1-WAVE2-Arp2/3 通路蛋白和 F-肌动蛋白向 G-肌动蛋白的比值的表达，促进焦点黏附的形成。DB 中的 loureirin C 对 SMG 处理的 Caco-2 细胞上皮屏障损伤有保护作用。DB 可防止 SMG 引起的 IEB 功能障碍，其机制与 Rac1-WAVE2-Arp2/3 通路介导的焦点黏附形成有关，有利于肠道上皮细胞迁移和屏障修复。
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