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白芍总苷通过调控 IL-23/IL-17 轴和 Th17/Treg 平衡防治炎症性肠病。

Total Glycosides of Peony Protects Against Inflammatory Bowel Disease by Regulating IL-23/IL-17 Axis and Th17/Treg Balance.

机构信息

* Zhejiang Cancer Hospital, Hangzhou 310022, P. R. China.

† School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, P. R. China.

出版信息

Am J Chin Med. 2019;47(1):177-201. doi: 10.1142/S0192415X19500095. Epub 2019 Jan 7.

DOI:10.1142/S0192415X19500095
PMID:30612460
Abstract

Inflammatory bowel disease (IBD) is a group of autoimmune diseases, including ulcerative colitis and Crohn's disease, characterized by nonspecific inflammation in the gut. Total glycoside of peony (TGP) has been widely used for treatment of autoimmune diseases because of its pharmacological effects. However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD. Hence, the aim of this study was to investigate the effects of TGP on experimental colitis mice and the related mechanisms. In the present study, we demonstrated that administration of TGP effectively attenuates colonic inflammation of TNBS-induced colitis mice, mainly reflected in significantly improved clinical parameters, reduced inflammatory response and myeloperoxidase (MPO) activity, even stronger systemic immune ability and effective improvement of Th17/Treg immune disorders. In addition, there was a stronger immunosuppressive ability in a positive cluster of differentiation 4 (CD4 ) T-lymphocytes from the TGP treated mouse colon, characterized by the inhibition of high levels of inflammatory factors and increased regulatory T cells. Importantly, high-dose TGP has similar therapeutic effects as salicylazosulfapyridine (SASP) on IBD treatment. The potential mechanisms might be, at least in part, related to the adjustment of imbalance of Th17/Treg cells and the inhibition of IL-23/IL17 inflammatory signal axis.

摘要

炎症性肠病(IBD)是一组自身免疫性疾病,包括溃疡性结肠炎和克罗恩病,其特征是肠道的非特异性炎症。芍药总苷(TGP)因其药理作用而被广泛用于治疗自身免疫性疾病。然而,TGP 是否通过调节辅助性 T 细胞 17 细胞(Th17)/T 调节细胞(Treg)免疫平衡或白细胞介素 23(IL-23)/IL-17 轴来实现治疗 IBD 的目标,缺乏深入的研究。因此,本研究旨在探讨 TGP 对实验性结肠炎小鼠的作用及其相关机制。在本研究中,我们证明了 TGP 给药可有效减轻 TNBS 诱导的结肠炎小鼠的结肠炎症,主要表现在临床参数显著改善,炎症反应和髓过氧化物酶(MPO)活性降低,甚至更强的全身免疫能力和有效的 Th17/Treg 免疫紊乱改善。此外,TGP 处理的小鼠结肠中的 CD4+T 淋巴细胞中存在更强的免疫抑制能力,其特征是抑制高水平的炎症因子和增加调节性 T 细胞。重要的是,TGP 的高剂量治疗对 IBD 的治疗与柳氮磺胺吡啶(SASP)具有相似的疗效。潜在的机制可能至少部分与 Th17/Treg 细胞失衡的调节和 IL-23/IL17 炎症信号轴的抑制有关。

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