Combined treatment with Rg1 and adipose-derived stem cells alleviates DSS-induced colitis in a mouse model.
Combined treatment with Rg1 and adipose-derived stem cells alleviates DSS-induced colitis in a mouse model.
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Rg1 和脂肪干细胞联合治疗可减轻小鼠模型中 DSS 诱导的结肠炎
DOI：
10.1186/s13287-022-02940-x
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发表时间：
2022-06-21
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
炎症性肠病，包括克罗恩病和溃疡性结肠炎，构成慢性炎症性病症，其可能损害整个胃肠道以及结肠粘膜。目前，IBD没有治疗性干预措施，所有可用的治疗方法都有副作用，限制了它们的使用。脂肪干细胞（ADSC）治疗是IBD的一种前瞻性治疗选择。先前的研究结果表明，Rg 1通过抑制LPS与巨噬细胞上的TLR 4结合并恢复Th 17/Treg比率来抑制炎症性疾病如结肠炎。本工作的目的是研究Rg 1是否可以增加ADSC在葡聚糖硫酸钠（DSS）引发的结肠炎小鼠模型中的影响。ADSC静脉接种到DSS引发的结肠炎小鼠中，而Rg 1通过口服灌胃递送。通过体重、结肠长度沿着和H&E染色评估结肠炎症。使用ELISA测量血清细胞因子水平。采用流式细胞仪检测脾脏免疫细胞百分率及免疫荧光指数（FMI）。通过免疫荧光评估Rg 1和ADSC同时处理对TLR 4-MyD 88信号传导的影响。Rg 1和ADSC有效地减轻了结肠炎症、体重减轻和结肠长度减少沿着组织学评分的影响。Rg 1和ADSC治疗降低了促炎细胞因子IL-1β、TNF-α、IL-6、IL-4和IL-17 A的血清水平，并上调了免疫抑制细胞因子IL-10的水平。与ADSC或Rg 1单独处理相比，Rg 1与ADSC联合处理显著改善了微生物群落结构。此外，Rg 1加ADSC治疗选择性地提高了脾调节性T（Treg）细胞的水平，下调了辅助性T细胞17型（Th 17）细胞的比例，表明肠道内稳态的恢复。此外，我们确定ADSC + Rg 1的组合比ADSC或Rg 1单独更有效地恢复免疫平衡，说明Rg 1对肠道微生物群的调节功能可能增强ADSC在恢复免疫平衡中的影响。ADSC联合Rg 1可下调TLR 4和MyD 88的表达，从而抑制TLR 4-MyD 8信号通路。免疫荧光结果还表明，Rg-1和ADSC的联合治疗可能优化IBD的治疗策略。在这里，我们发现Rg 1和ADSC的组合在小鼠模型中比单独ADSC更有效地抑制DSS诱导的结肠炎，表明Rg 1增强了ADSC对结肠炎的作用。在线版本包含补充材料，可通过10.1186/s13287-022-02940-x获得。
Inflammatory bowel diseases, consisting of Crohn’s disease and ulcerative colitis constitute chronic inflammatory conditions that may compromise the whole gastrointestinal tract as well as the colonic mucosa. Currently, there are no curative interventions for IBD, and all available treatments have side effects that limit their use. Adipose-derived stem cell (ADSC) treatment is a prospective treatment option for IBD. Previous findings indicated that ginsenoside (Rg1) dampened inflammatory diseases like colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg ratio. The purpose of this work was to investigate whether Rg1 can increase the influence of ADSC in a mouse model of colitis triggered by dextran sulfate sodium (DSS). ADSC was intravenously inoculated into mice with DSS-triggered colitis, while Rg1 was delivered via oral gavage. Colon inflammation was assessed via body weight, colon length along with H&E staining. Serum cytokine levels were measured using ELISA. Besides, flow cytometry was adopted to determine the percentage, as well as FMI of immune cells in the spleen. The effects of simultaneous Rg1 and ADSC treatment on TLR4-MyD88 signaling were assessed via immunofluorescence. Rg1 and ADSC effectively alleviated the impacts of colon inflammation, weight loss, and colon length reduction along with histological score. Treatment with Rg1 and ADSC reduced serum levels of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-4, and IL-17A and upregulated the level of immunosuppressive cytokine, IL-10. Compared with ADSC or Rg1 alone, combined treatment with Rg1 and ADSC significantly improved the structure of microbial community. Additionally, treatment with Rg1 plus ADSC selectively elevated the level of splenic regulatory T (Treg) cells and downregulated the proportion of T helper type 17 (Th17) cells, indicating restoration of intestinal homeostasis. Besides, we established that the combination of ADSC + Rg1 restored immunological balance more effectively than either ADSC or Rg1 alone, illustrating that Rg1's modulatory function on the gut microbiota may boost the impact of ADSCs in restoration of the immune balance. ADSC combined with Rg1 might downregulate the expression of TLR4 and MyD88, thereby suppressing TLR4-MyD8 signaling. The immunofluorescence results also suggested that co-therapy with Rg-1 and ADSC may optimize treatment strategies of IBD. Here, we find that the combination of Rg1 and ADSC alleviates DSS-induced colitis in a mouse model more efficiently than ADSC alone, indicating that Rg1 enhances the effect of ADSC against colitis. The online version contains supplementary material available at 10.1186/s13287-022-02940-x.
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DOI：
10.3390/antiox9100988
发表时间：
2020-10-14
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Kim J;Choi JH;Ko G;Jo H;Oh T;Ahn B;Unno T
通讯作者：
Unno T
间充质干细胞刺激肠道干细胞修复辐射引起的肠道损伤。
影响因子：
9
作者：
通讯作者：
--
影响因子：
9.3
作者：
Li, Cailan;Ai, Gaoxiang;Su, Ziren
通讯作者：
Su, Ziren
影响因子：
--
作者：
Bao, Cuifen;Wang, Yan;Liu, Xia
通讯作者：
Liu, Xia
影响因子：
29.7
作者：
Kaser A;Zeissig S;Blumberg RS
通讯作者：
Blumberg RS