溃疡性结肠炎(UC)表现为病因复杂且复发性的胃肠道疾病。肠神经系统(ENS)在纠正和协调肠道炎症反应中起着关键作用。小檗碱,一种异喹啉生物碱,在实验性结肠炎中被称为抗炎和治疗作用。然而,很少有研究关注其对ENS的调节功能。因此,我们着手探讨神经源性炎症在UC中的病理作用以及小檗碱对神经免疫相互作用的调节作用。肠胶质细胞(EGCs)的功能缺陷,胶质纤维酸性蛋白(GFAP)减少,P物质表达增加,在DSS诱导的小鼠UC中观察到。小檗碱的给药可明显改善UC的病情严重程度,恢复UC的黏膜屏障稳态。密切伴随着维持EGC的驻留和减轻炎症浸润和免疫细胞过度活化。体外,小檗碱对EGCs的单一培养具有直接保护作用,骨髓来源的树突状细胞(BMDCs),T细胞,和模拟炎症条件下的肠上皮细胞(IECs)。此外,小檗碱可以调节共培养系统中肠道EGCs-IECs-免疫细胞的相互作用。总之,我们的研究表明,EGCs-IECs-免疫细胞相互作用可能是黏膜炎症的关键范例,并提供了小檗碱调节肠神经性炎症的输注机制.
Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. However, little research focused on its regulatory function on ENS. Therefore, we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions. Functional defects of enteric glial cells (EGCs), with decreased glial fibrillary acidic protein (GFAP) and increased substance P expression, were observed in DSS-induced murine UC. Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC, closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation. In vitro, berberine showed direct protective effects on monoculture of EGCs, bone marrow-derived dendritic cells (BMDCs), T cells, and intestinal epithelial cells (IECs) in the simulated inflammatory conditions. Furthermore, berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems. In summary, our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.