急性胰腺炎(AP)是一种常见的急腹症，我院采用院内制剂——清胰颗粒防治AP重症化的临床疗效确切，但作用机制不明确限制了其临床推广。研究报道肠道菌群紊乱与AP严重程度密切相关，且色氨酸肠菌代谢物吲哚及吲哚酸(Indoles)作为AhR外源性配体，具有重要的免疫调节功能。我们前期研究发现AP大鼠体内存在Indoles生成减少及肠AhR/NLRP3信号通路抑制；清胰颗粒可以纠正AP大鼠肠菌紊乱，减少胰腺和结肠病损及炎症因子释放。由此，我们提出科学假说：肠道菌群紊乱介导色氨酸代谢物Indoles生成减少，导致肠AhR/NLRP3信号通路调控机体免疫应答失衡，诱导AP重症化；清胰颗粒能够恢复Indoles/AhR/NLRP3轴的信号转导抑制AP重症化。本项目拟以肠道菌群紊乱介导体内代谢异常在AP免疫应答中的作用探讨清胰颗粒的干预机制，系统诠释清胰颗粒抑制AP重症化的现代生物学基础，促进中医药国际化。

Acute pancreatitis (AP) is a common acute abdominal disease; and our hospital preparation-Qingyi Keli has positive effects on inhibition of AP exacerbation, but unclear mechanism limits its clinical dissemination. Studies had reported that gut microbiota disorder is closely related to the severity of AP; and indole and indole acid (Indoles), the tryptophan metabolites, have significant immunoregulatory functions as AhR exogenous ligands. Our previous research also found that AP caused down-regulation of Indoles production and inhibition of AhR/NLRP3 signaling pathway in rat gut. Moreover, Qingyi Keli corrected gut microbiota disorder in AP rats, and reduced pancreatic and colonic lesions as well as the release of inflammatory factors. Therefore, we propose a scientific hypothesis: Gut microbiota disorder causes down-regulation of tryptophan metabolites-Indoles, and leads to the imbalance of intestinal AhR/NLRP3 signaling mediated immune response, which finally induces AP exacerbation; and Qingyi Keli can correct the signal transduction of Indoles/AhR/NLRP3 axis and thereby inhibit AP exacerbation. The purpose of this project is to explore the intervention mechanism of Qingyi Keli basing on the effects of gut microbiota disorder on immune response in AP. This will systematically explain modern biological basis of Qingyi Keli inhibiting AP exacerbation, and further promote the internationalization of traditional Chinese medicine.