TRAF6-NF-κB信号通路调控胆源性胰腺炎小鼠的MMPs的表达和氧化应激反应

doi:10.3969/j.issn.1006-6233.2025.03.04

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Abstract Objective: To investigate the regulatory role of the tumor necrosis factor receptor-associated factor 6 (TRAF6)-nuclear factor κB (NF-κB) signaling pathway in mice with biliary pancreatitis, particularly its effects on the expression of matrix metalloproteinases (MMPs) and oxidative stress response. Methods: Twenty-four adult male C57BL/6J mice were randomly divided into three groups, with eight mice in each group: normal group (Group I), model group (Group II), and model + C25-140 group (Group III). C25-140 is a specific inhibitor of TRAF6 and NF-κB activity. The pancreatic organ-body ratio was measured in each group. Western blot was used to detect the expression of TRAF6, NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), MMP-2, and MMP-9 in pancreatic tissue. Additionally, levels of IL-1β, IL-6, TNF-α, α-amylase, and lipase in the serum were measured using enzyme-linked immunosorbent assay (ELISA) or kit methods. Results: Compared to Group I, Group II showed a significant increase in the pancreatic organ-body ratio (P<0.05), as well as significantly higher levels of IL-1β, IL-6, TNF-α, α-amylase, and lipase in both pancreatic tissue and serum (all P<0.05). Compared to Group II, these indicators were significantly lower in Group III (all P<0.05). TRAF6 and p-NF-κB p65 expressions were significantly upregulated in Group II compared to Group I (both P<0.05), while NF-κB p65 expression showed no significant difference (P>0.05). Group III showed significant downregulation of TRAF6 and p-NF-κB p65 compared to Group II (both P<0.05), with no significant difference in NF-κB p65 expression (P>0.05). MMP-2 and MMP-9 expressions in pancreatic tissue were significantly upregulated in Group II compared to Group I (both P<0.05). Group III showed significant downregulation of MMP-2 and MMP-9 compared to Group II (both P<0.05). Levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly increased, whereas superoxide dismutase (SOD) levels were significantly decreased in Group II compared to Group I (all P<0.05). In contrast, ROS and MDA levels were significantly decreased, and SOD levels were significantly increased in Group III compared to Group II (all P<0.05). Conclusion: The TRAF6-NF-κB signaling pathway plays an important regulatory role in the inflammatory response, MMP-2 and MMP-9 expression, and oxidative stress response in mice with biliary pancreatitis. The specific inhibitor C25-140 alleviates the inflammatory response, reduces MMPs expression, and mitigates oxidative stress response in these mice by inhibiting the TRAF6-NF-κB signaling pathway.

Key words： TRAF6-NF-κB signaling pathway Biliary pancreatitis Oxidative stress Matrix metalloproteinases

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.03.04 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I3/374

[1] Al Taweel B,Tzedakis S,Panaro F.Early cholecystectomy cannot be regarded as a mortality risk factor in moderate and severe acute biliary pancreatitis [J].Hepatobiliary Surg Nutr,2024,13(1):109-111.
[2] Hu F,Lou N,Jiao J,et al.Macrophages in pancreatitis:mechanisms and therapeutic potential [J].Biomed Pharmacother,2020(131):110693.
[3] Liu Y,Meng Y,Zhou C,et al.Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity [J].BMC Neurosci,2023,24(1):14.
[4] Sun J,Zhao B,Du K,et al.TRAF6 correlated to invasion and poor prognosis of glioblastoma via elevating MMP9 expression [J].Neuroreport,2019,30(2):127-133.
[5] Salau VF,Erukainure OL,Koorbanally NA,et al.Ferulic acid promotes muscle glucose uptake and modulate dysregulated redox balance and metabolic pathways in ferric-induced pancreatic oxidative injury[J].Food Biochem,2022,46(4):13641.
[6] Sternby H,Hartman H,Thorlacius H,et al.The initial course of IL1β,IL-6,IL-8,IL-10,IL-12,IFN-γ and TNF-α with regard to severity grade in acute pancreatitis [J].Biomolecules,2021,11(4):591.
[7] Mikhalchik E,Basyreva L Y,Gusev S A,et al.Activation of neutrophils by mucin-vaterite microparticles [J].Int Mol Sci,2022,23(18):10579.
[8] Feng D,Guo R,Liao W,et al.Plantamajoside alleviates acute sepsis-induced organ dysfunction through inhibiting the TRAF6/NF-κB axis [J].Pharm Biol,2023,61(1):897-906.
[9] Zheng C,Ji Z,Xu Z,et al.Overexpression of miR-146a-5p ameliorates inflammation and autophagy in TLCs-Induced AR42J cell model of acute pancreatitis by inhibiting IRAK1/TRAF6/NF-κB pathway [J].Ann Clin Lab Sci,2022,52(3):416-425.
[10] Ling L,Li Y,Li H,et al.MMP-2 and MMP-9 gene polymorphisms act as biological indicators for ulinastatin efficacy in patients with severe acute pancreatitis [J].Medicine,2019,98(24):15831.
[11] Mo Y,Zhang X,Lao Y,et al.Fentanyl alleviates intestinal mucosal barrier damage in rats with severe acute pancreatitis by inhibiting the MMP-9/FasL/Fas pathway [J].Immunopharmacol Immunotoxicol,2022,44(5):757-765.