基于色氨酸代谢探讨艾灸治疗肠易激综合征的外周与中枢作用机制

近期研究表明：色氨酸代谢与肠易激综合征（IBS）关系密切，肠道菌群可能通过调节色氨酸代谢，介导IBS内脏痛、抑郁、焦虑发病的关键环节。申请人前一个已结题的国家自然科学基金项目表明：艾灸治疗IBS疗效确切，且可调节IBS大鼠血清色氨酸代谢。本研究在前期基础上，拟开展：1）临床与动物实验相结合，研究艾灸对IBS患者血清和IBS模型小鼠结肠、血清、海马、下丘脑5-HT通路与犬尿氨酸通路色氨酸代谢，以及消化道症状、抑郁、焦虑等的影响，探讨艾灸调控色氨酸代谢治疗IBS的外周和中枢作用机制；2）结合基因敲除技术，采用TPH1基因敲除小鼠、IDO1基因敲除小鼠，揭示艾灸调控色氨酸代谢治疗IBS的关键靶点；3）结合16S rRNA 高通量测序及生物信息学分析技术，运用益生菌、抗生素双向干预IBS模型小鼠，从肠道菌群调控色氨酸代谢角度，深入探讨艾灸治疗IBS的作用机制，为艾灸治疗IBS提供新的科学依据。

Researches show tryptophan metabolic is closely related to irritable bowel syndrome (IBS), gut microbiota may regulate tryptophan metabolism to mediate the key links of IBS visceral pain, depression and anxiety. Our research, supported by national natural science foundation of China (NSFC), indicated that moxibustion treatment had good effect on IBS and regulated serum tryptophan metabolism of IBS rats. Based on previous researches, 1) we will combine clinical and animal experiments, via 5-HT pathway and kynurenine pathway, to study the effect of moxibustion on tryptophan metabolism in serum of IBS patients，and colon, serum, hippocampus and hypothalamus of IBS model mice, and the effect of moxibustion on gastrointestinal symptoms, depression and anxiety of IBS patients and IBS model mice, and explore the peripheral and central mechanism of moxibustion regulating tryptophan metabolism in treating IBS; 2) we will take in gene knockout technology, use the TPH1 knockout mice and IDO1 gene knockout mice, to reveal the key targets of moxibustion regulating tryptophan metabolism in treating IBS; 3) we will adopt 16 s rRNA high-throughput sequencing and bioinformatics analysis technology, use probiotics and antibiotics on IBS model mice, to explore the mechanism of moxibustion in treating IBS from the perspective of gut microbiota regulating tryptophan metabolism, to provide new scientific basis for moxibustion treating IBS.