体内
急性胰腺炎
炎症
药理学
医学
腺泡细胞
体外
细胞凋亡
胰腺炎
化学
免疫学
内科学
生物
生物化学
生物技术
作者
Xiao Han,Jingpiao Bao,Jiahua Ni,Bin Li,Pengli Song,Rong Wan,Xingpeng Wang,Guoyong Hu,Congying Chen
标识
DOI:10.1016/j.jep.2024.117750
摘要
Herbal formulas from Traditional Chinese Medicine are common and well-established practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation. This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved. Major compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis level were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrolment. Nine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP model in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnfα, Il1β and Il6 were significantly lower after QXJYF treatment compared to M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDHα levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly inhibit CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and prevent pSAP patients from progressing to SAP. QXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis.
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