从表观遗传修饰探讨腹泻型肠易激综合征肝郁脾虚的机制

Study on the mechanism of liver depression and spleen deficiency in diarrhea dominant irritable bowel syndrome from epigenetic modification

腹泻型肠易激综合征(IBS-D)是消化科常见病和疑难病,临床以对症治疗为主,但治疗后易复发,患者长期生活质量低下。肝郁脾虚是IBS-D的核心病机,“痛泻”是肝郁脾虚证的主要临床表现,与内脏高敏感性关系密切。内脏高敏感性是IBS-D的病理生理基础之一,中枢敏化是其形成的关键途径。近年来研究发现,表观遗传修饰可调控中枢敏化的诱导、形成和维持环节,对内脏高敏感性的形成有重要影响,具体分子机制可概括为5-羟色胺受体3(5-HT3R)基因低水平DNA甲基化促进中枢敏化诱导环节,和(或)神经肽Y(NPY)基因低水平的组蛋白乙酰化导致中枢敏化去抑制,进而持续激活细胞外调节蛋白激酶(ERK)1/2和c-fos引起内脏高敏感性。就此探讨IBS-D肝郁脾虚与异常的表观遗传修饰介导的IBS-D内脏高敏感性相关,探讨IBS-D肝郁脾虚的表观遗传学内涵及痛泻要方作用机制,对保持中医药优势具有重要意义。

Diarrhea dominant irritable bowel syndrome(IBS-D)is a common and difficult disease in digestive department,and it is mainly symptomatic treatment clinically,but it is easy to relapse after treatment,and the patients’long-term quality of life is low.Liver stagnation and spleen deficiency is the core pathogenesis of IBS-D.‘Pain and diarrhea’is the main clinical manifestation of liver stagnation and spleen deficiency syndrome,which is closely related to visceral hypersensitivity.Visceral hypersensitivity is one of the pathophysiological mechanism of IBS-D,and the central sensitization is the key way of its formation.Recently,some studies have found that epigenetic modification can regulate the induction,formation and maintenance of central sensitization,and it has an important impact on the formation of visceral hypersensitivity,the specific molecular mechanism can be summarized as follows:the low-level DNA methylation of 5-HT3R gene promotes the induction of central sensitization,and/or the low-level histone acetylation of NPY gene leads to the disinhibition of central sensitization.Further,continuous activation of ERK1/2 and c-fos cause visceral hypersensitivity.Therefore,it is of great significance to explore the relationship between liver stagnation and spleen deficiency in IBS-D and the visceral hypersensitivity mediated by abnormal epigenetic modification,and to explore the epigenetic connotation of liver stagnation and spleen deficiency in IBS-D and the mechanism of action of the key prescription of pain and diarrhea,so as to maintain the advantages of traditional Chinese medicine.