基于Th17/Treg平衡和IL-23/IL-17炎症轴探讨麸炒白芍总苷治疗炎症性肠病的作用机制

Inflammatory bowel disease (IBD) is an inflammatory bowel disease of anomaly caused by intestinal mucosal immune system. Radix Paeoniae Alba has anti-inflammatory and immunomodulatory effects, our previous study found that total glycosides in radix paeoniae alba after stir-baking with bran can significantly reduce inflammatory symptoms of IBD, has good anti IBD effect, but its mechanism is still not clear. Further study found that, Th17/Treg balance to maintain physiological intestinal inflammation, especially increase of proportion of Th17 can cause pathological intestinal inflammation; and IL-23/IL-17 axis activation can be further enlarged inflammation caused by the imbalance of Th17/Treg reaction, resulting in the pathogenesis of IBD. In view of this, we put forward the hypothesis: total glycosides in radix paeoniae alba after stir-baking with bran play a role in the treatment of IBD by regulating the balance of Th17/Treg and IL-23/IL-17 in inflammatory shaft. The project intends to establish a rat model of IBD and carry out an anti-IBD study, and combined with in vitro cell experiment, to explore total glycosides in bran Fried radix paeoniae alba’s effect on the regulation of Th17/Treg balance and IL-23/IL-17 inflammation axis. This project is expected to clarify the pharmacodynamic material basis of bran fried radix paeoniae alba anti-IBD effect and benefit the Radix Paeoniae Alba anti-inflammatory in clinical treatment.

炎症性肠病（IBD）是一种由肠道黏膜免疫系统异常引起的肠道炎症性疾病。白芍具有抗炎与免疫调节的功效，课题组前期发现麸炒白芍总苷可显著减轻IBD炎性症状，具有良好的抗IBD作用，但其作用机制尚不清楚。进一步研究发现，Th17/Treg平衡维持着肠道的生理性炎症，这一平衡的打破尤其是Th17的比例提高导致了肠道病理性炎症的发生；而IL-23/IL-17炎症轴继发性激活可进一步放大Th17/Treg失衡所致的炎症反应，导致IBD发病。鉴此，本课题提出假说：麸炒白芍总苷通过调节Th17/Treg平衡和IL-23/IL-17炎症轴发挥治疗IBD的作用。本项目拟采用IBD大鼠考察麸炒白芍总苷抗IBD的疗效，并结合体外细胞实验，探究麸炒白芍总苷对Th17/Treg平衡和IL-23/IL-17炎症轴的调节作用，揭示其抗IBD的作用机制。本研究有望阐明麸炒白芍抗IBD的药效物质基础，裨益白芍抗炎的临床治疗。

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，其特征是肠道内有非特异性炎症。白芍总苷具有良好的药理作用，已广泛应用于自身免疫性疾病的治疗。然而，TGP是否能调节Th17/Treg免疫平衡或IL-23/IL-17轴来达到治疗IBD的目的还不够深入。因此，本研究的目的是研究白芍总苷对实验性结肠炎小鼠的作用及其相关机制，在本研究中，我们证明白芍总苷能有效地减轻TNBS诱导的结肠炎小鼠的色素性炎症，主要表现在显著改善临床参数，降低炎症反应和MPO活性，更强的系统免疫能力，有效改善Th17/Treg免疫紊乱。此外，TGP处理小鼠结肠的CD4+T淋巴细胞具有更强的免疫抑制能力，其特点是抑制高水平的炎症因子和增加的调节性T细胞。重要的是，大剂量TGP对IBD的治疗效果与SASP相似，其潜在机制可能至少部分与调节Th17/Tregcells失衡和抑制IL-23/IL17炎症信号轴有关。