Total glucosides of Paeony restores intestinal barrier function through inhibiting Lyn/Snail signaling pathway in colitis mice
Total glucosides of Paeony restores intestinal barrier function through inhibiting Lyn/Snail signaling pathway in colitis mice
复制标题
DOI：
10.1016/j.phymed.2021.153590
复制
发表时间：
2021-05-23
期刊：
影响因子：
7.9
通讯作者：
Shen, Xiao-Yan
中科院分区：
文献类型：
--
作者：
Cao, Xin-Yue;Ni, Jia-Hui;Shen, Xiao-Yan
背景：炎症性肠病（IBD）是一种自身免疫性疾病。IBD发病机制复杂，肠黏膜屏障损伤被认为是IBD发病和复发的触发因素。白芍总苷（TGP）在临床研究中显示出良好的免疫炎症抑制作用。然而，其对IBD的作用和机制在很大程度上是未知的。目的：探讨TGP对IBD的作用及机制。研究设计：采用dss诱导结肠炎小鼠模型。TGP通过灌胃给予。采用外膜囊泡（OMV）刺激Caco-2细胞建立体外模型。方法：将C57BL/6小鼠分为正常对照组、模型组、美萨拉嗪组、芍药苷（PA）组、TGP高剂量组和TGP低剂量组。2.5% DSS诱导模型7 d， TGP灌胃10 d。采用症状分析、组织化学分析、RT-qPCR和ELISA评价TGP的疗效。通过体内外肠通透性、免疫印迹和免疫荧光等方法探讨其作用机制。结果：我们的研究结果显示，TGP可以显著改善症状和病理改变，降低结肠组织和血清中tnf - α、IL-17A、IL-23和ifn - γ的水平，并呈剂量依赖性。TGP还能在体内外降低肠通透性，恢复肠上皮细胞紧密连接蛋白和粘附连接蛋白的表达。此外，TGP可以抑制p-Lyn和Snail的表达，阻止Snail的核定位，从而保持紧密和粘附的连接。结论：TGP可有效改善dss诱导的小鼠结肠炎的症状，并通过抑制Lyn/Snail信号通路保护肠上皮屏障，可能是治疗IBD的理想药物。
Background: Inflammatory bowel disease (IBD) is an autoimmune disease. The pathogenesis of IBD is complicated and intestinal mucosal barrier damage is considered as the trigger factor for the initiation and recurrence of IBD. Total Glucosides of Paeony (TGP) has shown good inhibitory effects on immune-inflammation in clinic studies. However, its effect and mechanism on IBD are largely unknown.Purpose: The purpose of this study is to evaluate the effect and mechanism of TGP on IBD.Study design: DSS-induced colitis mouse model was used. TGP was given by gavage. Caco-2 cells were stimulated by outer membrane vesicles (OMV) to establish an in vitro model.Methods: C57BL/6 mice were divided into normal control group, model group, mesalazine group, paeoniflorin (PA) group, high-dose group of TGP, and low-dose group of TGP. The model was induced with 2.5% DSS for 7 days, and TGP was intragastrically administered for 10 days. The therapeutic effect of TGP was evaluated by symptoms, histochemical analysis, RT-qPCR and ELISA. The mechanism was explored by intestinal permeability, Western blot and immunofluorescence in vivo and in vitro.Results: Our results showed that TGP could significantly improve the symptoms and pathological changes, with reduced levels of TNF-alpha, IL-17A, IL-23 and IFN-gamma in the colon tissues and serum under a dose-dependent manner. TGP also reduced the intestinal permeability and restored the protein expression of tight junction and adherens junction proteins of intestinal epithelial cells in vivo and in vitro. Furthermore, TGP could inhibit the expression of p-Lyn and Snail and prevent Snail nuclear localization, thereby maintaining tight and adherens junctions.Conclusion: TGP effectively improves the symptoms of DSS-induced colitis in mice, protects the intestinal epithelial barrier by inhibiting the Lyn/Snail signaling pathway, and maybe a promise therapeutic agent for IBD treatment.