痛泻要方调控铁死亡介导的MC/COX2/PGE2信号轴在IBS-D内脏高敏感中的作用机制研究

内脏高敏感是IBS-D的核心发病机制。而结肠黏膜肥大细胞铁死亡介导的MC/COX2/PGE2通路在IBS-D内脏高敏感的发展中起关键作用。前期研究表明痛泻要方可以抑制肥大细胞脱颗粒释放MCT、组胺，NO等炎性细胞因子，改善内脏高敏感，但其是否通过抑制铁死亡以调控其下游MC/COX2/PGE2通路来发挥作用还有待进一步研究。本项目将从肝郁脾虚型IBS-D大鼠和大鼠骨髓来源肥大细胞脱颗粒模型两个水平证实IBS-D中肥大细胞发生铁死亡现象，阐明铁死亡是肥大细胞参与IBS-D内脏高敏感发生的重要死亡形式，并以铁死亡介导MC/COX2/PGE2通路为切入点，采用荧光探针监测，qRT-PCR等检测手段，探讨痛泻要方改善IBS-D内脏高敏感的分子机制，为实现中医药的精准医疗提供科学的验证依据。

Visceral hypersensitivity is the core pathogenesis of IBS-D.Ferroptosis-mediated MC/COX2/PGE2 pathway may play a key role in the development of visceral hypersensitivity in IBS-D. Previous studies have shown that Tongxieyaofang can inhibit the mediators from mast cells degranulation such as MCT, Histamine, NO and other inflammatory cytokines, which reduce visceral hypersensitivity. however, it remains to be further studied whether it plays a role by inhibiting ferroptosis and regulating the downstream MC/COX2/PGE2 pathway. In this study, ferroptosis of mast cells in IBS-D will be confirmed from the levels of liver depression and spleen deficiency IBS-D rats model and the mast cells model derived from rat bone marrow.ferroptosis-mediated MC/COX2/PGE2 pathway was used as the cut-in point to prove that ferroptosis is an important form of mast cells death involved in visceral hypersensitivity of IBS-D.Fluorescence probe and qRT-PCR were used to detect ferroptosis, to explore the molecular mechanism of Tongxieyaofang inhibiting visceral hypersensitivity of IBS-D, and to provide scientific evidence for accurate treatment of traditional Chinese medicine.