Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, China.
Cell Rep Med. 2023 Dec 19;4(12):101304. doi: 10.1016/j.xcrm.2023.101304. Epub 2023 Nov 29.
Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.
胆汁酸在急性胰腺炎（AP）患者中发生改变，并与预后相关。在这里，我们进行了靶向代谢组学分析，以检测 AP 急性期（n=326）和恢复期（n=133）患者以及健康对照者（n=60）的胆汁酸变化。鹅脱氧胆酸（CDCA）在急性期减少，在恢复期增加，并与胰腺坏死有关。CDCA 和其衍生物奥贝胆酸在体外显示出对腺泡细胞损伤和小鼠模型中胰腺坏死的保护作用，RNA 测序显示氧化磷酸化途径主要参与其中。此外，我们发现法尼醇 X 受体（FXR，CDCA 受体）的过表达可抑制胰腺坏死，而 FXR 的干扰表达在小鼠中表现出相反的表型。我们的研究结果可能提示靶向 CDCA 是治疗 AP 腺泡细胞坏死的一种潜在策略，但需要进一步验证。
