QingXia HuaYu Formula Alleviates Severe Acute Pancreatitis-Associated Intestinal Injury by Modulating Group 3 Innate Lymphoid Cells

清夏化玉方通过调节第3组固有淋巴细胞缓解重症急性胰腺炎相关肠道损伤

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作者:Yuyang Liu ,Yishuang Tang ,Yue Wu ,Yujie Jiang ,Liang Zhang ,Mingxian Zheng ,Yixuan Ye ,Jing Kong ,Xiaosu Wang ,Lin Yuan ,Feng He ,Bingduo Zhou

Abstract

Background: Severe acute pancreatitis (SAP), one of the common causes of acute abdomen in clinical practice, is characterized by acute and rapid onset as well as the systemic inflammatory response syndrome, which often leads to intestinal injury and high mortality. Recent studies indicate that innate lymphoid cells (ILCs) play an important role in the connection of SAP and intestinal injury. TCM, including the QingXia HuaYu (QXHY) formula, is known to benefit gastrointestinal dysfunction in SAP, but its mechanisms, especially regarding ILCs, are unclear. Methods: A mouse model of SAP was established by retrograde infusion of sodium taurocholate into the common bile duct of C57BL/6 mice. QXHY was orally administered three times postinfusion. Serum inflammatory markers, pancreatic myeloperoxidase, and histopathological changes in the mice with SAP with or without QXHY treatment were used to evaluate the pancreatic injury and the therapeutic effects of QXHY. Intestinal tight junctions, serum markers for mucosal injury, and inflammatory factors were used to analyze the effects of QXHY on intestinal injury in SAP mice. Flow cytometry and qRT-PCR were used to analyze ILC3s numbers and functions. Results: QXHY significantly reduced serum amylase, pancreatic myeloperoxidase, and improved histopathological manifestations in SAP mice. In addition, QXHY reduced intestinal damage, improved tight junction integrity, and lowered proinflammatory cytokines. Mechanistically, QXHY restored the diminished RORγt+-ILC3s in SAP mice and upregulated the expression of IL-22 (interleukin-22) and IL-17 (interleukin-17) mRNA. Conclusion: QXHY mitigates SAP-associated intestinal damage by enhancing ILC3 cells to regulate tissue injury and maintain homeostasis. Our data suggest that QXHY is a promising alternative and cost-friendly therapy for SAP-associated intestinal damage.

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