痛泻要方“抑木”组分白芍防风缓解IBS-D内脏高敏的肠道菌群——脑肠交互机制研究

Visceral hypersensitivity is the most essential pathological process of diarrhea-predominated irritable bowel syndrome (IBS-D), which is also a major cause of IBS-D symptoms. IBS-D symptoms induced by visceral hypersensitivity is highly consistent with diarrhea symptoms defined by Traditional Chinese Medicine with the theory-liver hyperactivity suppressing spleen. Our previous study showed that suppressing Mu with paenoiae alba and radix sileris relieves visceral hypersensitivity in IBS-D, and the effective is correlated with restoration of gut-brain interaction (high expression of BDNF in hippocampus versus low expression of it in colonic myenteric plexus). However, the mechanism that brings the differential expressions in hippocampus and colonic myenteric plexus is not clear. So we hypothesize that paenoiae alba and radix sileris repair the intestinal flora through regulating the miRNA expression in colonic epithelial cells and feces, and therefore they cause differential expression of BDNF in hippocampus and colonic myenteric plexus and thus restore the gut-brain interaction to ease visceral hypersensitivity. We will use methods of epigenetics, bioinformatics and molecular biology to test the hypothesis. Understanding the mechanism of paenoiae alba and radix sileris in relieving visceral hypersensitivity makes good sense in explaining the principle of “suppressing Mu to relieve diarrhea” and finding new targets for developing treatment options for IBS-D.

内脏高敏是IBS-D最重要的病理特征，也是诱发IBS-D主要症状的原因。内脏高敏所致的IBS-D症状与“肝木旺克脾土”所致泄泻症状高度一致。我们前期研究发现“抑木”组分白芍防风能缓解IBS-D内脏高敏，且该效应与促进脑肠双向良性互动有关（体现为BDNF在海马表达上调而在结肠肌间神经丛表达下调）。然而，目前未能回答白芍防风使BDNF在海马和结肠的差异化表达的调控机制。为此，我们提出假说“白芍防风组分可能通过调控结肠上皮细胞及粪便中miRNA表达实现肠道菌群结构良性调整，从而促使结肠肌间神经丛和海马的BDNFmRNA差异化表达实现脑肠良性互动从而缓解内脏高敏”，以肠道菌群—脑肠交互作为切入点，通过表观遗传学、生物信息学、分子生物学等多学科技术手段，明确白芍防风缓解内脏高敏的机制，对科学阐释中医学 “抑木止泻”的内涵和发掘治疗靶点提高临床疗效意义重大。

内脏高敏是IBS-D最重要的病理特征，也是诱发IBS-D主要症状的原因。内脏高敏所致的IBS-D症状与“肝木旺克脾土”所致泄泻症状高度一致。我们前期研究发现“抑木”组分白芍防风能缓解IBS-D内脏高敏，且该效应与促进脑肠双向良性互动有关（体现为BDNF在海马表达上调而在结肠肌间神经丛表达下调）。然而，目前未能回答白芍防风使BDNF在海马和结肠的差异化表达的调控机制。为此，我们提出假说“白芍防风组分可能通过调控结肠上皮细胞及粪便中miRNA表达实现肠道菌群结构良性调整，从而促使结肠肌间神经丛和海马的BDNFmRNA差异化表达实现脑肠良性互动从而缓解内脏高敏”，以肠道菌群—脑肠交互作为切入点，通过表观遗传学、生物信息学、分子生物学等多学科技术手段，证实了痛泻要方抑木组分白芍防风可以改善IBS-D模型大鼠的内脏高敏。其作用机制可能通过改善肠道菌群结构，调整脑肠BDNF差异性表达来实现，对科学阐释中医学 “抑木止泻”的内涵和发掘治疗靶点提高临床疗效意义重大。