清肠化湿方抑制NF-kB活化调控IL-6/STAT3通路治疗溃疡性结肠炎作用机制的研究

In recent years, with in-depth research on ulcerative colitis immune mechanism, it was found that excessive expression of NF-κB can activate downstream IL-6/STAT3 pathway, to further promote Th17 cell differentiation. Therefore, inhibit activity of NF-κB and regulate the expression of inflammatory cytokines, thus reducing the inflammatory response has become a new means of treatment. Preliminary studies show that: QingChangHuaShi Decoction can significantly improve the clinical symptoms of patients with ulcerative colitis. Its mechanism of action applys to inhibiting the expression of NF-κB in intestinal mucosa and reducing the generation and activation of Th17 cells. But the relationship to IL-6/STAT3 pathway needs to be further clarified. In this study, SASP and NF-κB inhibitor antisense oligodeoxynucleotide (ASODN) for the control of UC mice model in vivo experiments to observe the bowel dampness whether through down regulation of NF-κB mediated IL-6/STAT3 pathway, reduce inflammation. In order to further clarify the access mechanism and provide scientific basis for clinical medication.

近年来，随着对溃疡性结肠炎免疫机制研究的深入，发现NF-κB过度表达能激活下游IL-6/STAT3通路，促进CD4+T细胞向Th17分化。因此，抑制NF-κB的表达，下调相关信号通路，减少促炎因子分泌已成为治疗的新途径。前期研究表明：清肠化湿方能够显著改善溃疡性结肠炎患者的临床症状，减轻炎症反应，其作用机制与抑制肠黏膜组织NF-κB转录活性、减少Th17细胞的生成与分化有关，但与IL-6/STAT3通路的关系有待进一步阐明。本研究以柳氮磺胺吡啶（SASP）、NF-κB抑制剂反义寡核苷酸（ASODN）为对照，观察清肠化湿方是否通过抑制NF-κB介导的IL-6/STAT3通路，下调结肠黏膜炎症因子水平，发挥抗炎作用，以进一步阐明其通路机制，为临床用药提供科学依据。

溃疡性结肠炎(UC)是一种影响结肠黏膜的慢性炎症和癌前病变。近年来，该病在我国的发病率呈上升趋势，其确切的发病机制尚不清楚。近年来的研究发现过度的免疫反应，尤其是Th17细胞是炎性发生的重要因素。清肠化湿方作为临床治疗UC的常用方已获得较好的疗效。本研究通过脂多糖(LPS)刺激HT-29细胞的炎症细胞模型，以及三硝基苯磺酸(TNBS)诱导BALB/c小鼠模型，以柳氮磺胺吡啶（SASP）、NF-κB抑制剂反义寡核苷酸（ASODN）为对照，探讨清肠化湿方可能的作用机制。实验研究证明：清肠化湿方可以下调NF-kB / IL-6 / STAT3通路来减少Th17细胞的生成与分化，抑制促炎因子IL-17的表达，从而减轻UC的病情，为临床用药及溃疡性结肠炎中药新药的开发提供科学依据。