Ying Feng, Xinxin Jin, Haoyu Xu, Bo Sun, Meixia Guo, Minli Li
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引用次数: 0
摘要
本研究旨在探讨JAK2 (Janus kinase 2)/STAT3 （signal transducer and activator of transcription 3）信号在严重急性胰腺炎（SAP）肝损伤中的作用，重点研究胰腺弹性酶和脂多糖（LPS）诱导的Kupffer细胞（KC）活化。方法：采用胆总管逆行灌注牛磺胆酸法建立大鼠SAP模型。在肝组织中量化炎症细胞因子水平和JAK2/STAT3通路活性。KCs用弹性酶/LPS±AG490 （JAK2抑制剂）处理。分析促炎细胞因子、RNA和蛋白的表达。结果和讨论：SAP大鼠血清和肝组织中TNF-α、IL-6和IL-18水平升高，JAK2/STAT3通路激活。AG490抑制JAK2/STAT3激活，减少炎症，减轻肝损伤。同样，用弹性蛋白酶和LPS处理的KCs显示出促炎细胞因子水平升高和JAK2/STAT3上调，而AG490处理则减轻了这一现象。结论：这些发现强调了JAK2/STAT3信号通路在sap诱导的肝损伤中的关键作用。AG490选择性抑制该途径可减少炎症并保护肝脏免受损害，提示其可能成为炎症性肝病的治疗靶点。
Pancreatic Elastase Affects Liver Injury by Activating Pro-Inflammatory Cytokines in Kupffer Cells via the JAK2/STAT3 Signaling Pathway.
Introduction: This study aimed to investigate the role of JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) signaling in liver injury during severe acute pancreatitis (SAP), focusing on pancreatic elastase- and lipopolysaccharide (LPS)-induced Kupffer cell (KC) activation.
Methods: A rat SAP model was established via retrograde taurocholic acid infusion into the biliopancreatic duct. Inflammatory cytokine levels and JAK2/STAT3 pathway activity were quantified in liver tissues. KCs were treated with elastase/LPS ± AG490 (JAK2 inhibitor). Proinflammatory cytokines, RNA, and protein expression were analyzed.
Results and discussion: SAP rats exhibited elevated TNF-α, IL-6, and IL-18 levels in both serum and liver tissues, with JAK2/STAT3 pathway activation. AG490 administration suppressed JAK2/STAT3 activation, reduced inflammation, and alleviated liver injury. Similarly, KCs treated with elastase and LPS showed increased proinflammatory cytokine levels and JAK2/STAT3 upregulation, which were mitigated by AG490 treatment.
Conclusion: The findings highlighted the pivotal role of the JAK2/STAT3 signaling pathway in SAP-induced liver injury. Selective inhibition of this pathway by AG490 could reduce inflammation and protect against liver damage, suggesting its potential as a therapeutic target for inflammatory liver diseases.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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