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  

TRAF6-NF-κB Signaling Pathway Regulates the Expression of MMPs and Oxidative Stress Response in Mice with Biliary Pancreatitis

作　　者：古丽斯坦·阿布拉 胡佳丽 哈丽娜 卢加杰[1] 高峰[1] GULISITAN Abula;HU Jiali;HALINA(Xinjiang Uygur Autonomous Region People's Hospital/Xinjiang Clinical Medical Research Center for Digestive System Diseases,Xinjiang Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院消化内科/新疆消化系统疾病临床医学研究中心,新疆乌鲁木齐830000

出　　处：《河北医学》2025年第3期374-380,共7页Hebei Medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目,(编号:2023D01C317)。

摘　　要：目的:探讨肿瘤坏死因子受体相关因子6(TRAF6)-核因子κB(NF-κB)信号通路在胆源性胰腺炎小鼠中的调控作用和对基质金属蛋白酶(MMPs)表达和氧化应激反应的影响。方法:将24只成年C57BL/6J雄性小鼠随机分为3组,每组8只:正常组(Ⅰ组)、模型组(Ⅱ组)和模型+C25-140组(Ⅲ组)。C25-140为TRAF6和NF-κB活性的特异性抑制剂。检测各组小鼠胰腺脏体比。用Western blot法检测胰腺组织中TRAF6、NF-κB p65、磷酸化的NF-κB p65(p-NF-κB p65)、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶(MMP)-2、MMP-9的表达。另外,用酶联免疫吸附法或者试剂盒法检测小鼠血清中IL-1β、IL-6、TNF-α、α淀粉酶、脂肪酶的浓度。结果:与I组相比,Ⅱ组小鼠的胰腺脏体比显著上调(P<0.05),胰腺组织及血清中的白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)、α淀粉酶和脂肪酶浓度显著增高(均P<0.05)。与Ⅱ组相比,Ⅲ组小鼠的上述指标显著降低(均P<0.05)。与I组相比,Ⅱ组胰腺组织中TRAF6、p-NF-κB p65的表达显著上调(均P<0.05),而NF-κB p65的表达无显著差异(P>0.05)。与Ⅱ组相比,Ⅲ组中TRAF6、p-NF-κB p65的表达显著下调(均P<0.05),NF-κB p65的表达无显著差异(P>0.05)。与I组相比,Ⅱ组胰腺组织中MMP-2和MMP-9的表达显著上调(均P<0.05)。与Ⅱ组相比,Ⅲ组中MMP-2和MMP-9的表达显著下调(均P<0.05)。与I组相比,Ⅱ组胰腺组织中ROS和MDA水平显著上调,而SOD水平显著下调(均P<0.05)。与Ⅱ组相比,Ⅲ组中ROS和MDA水平显著下调,而SOD水平显著上调(均P<0.05)。结论:TRAF6-NF-κB信号通路在胆源性胰腺炎小鼠的炎症反应、MMP-2和MMP-9表达及氧化应激反应中起重要调控作用。特异性抑制剂C25-140通过抑制TRAF6-NF-κB信号通路,显著减轻了胆源性胰腺炎小鼠的炎症反应、降低了MMPs的表达和氧化应激反应。Objective:To investigate the regulatory role of the tumor necrosis factor receptor-associated factor 6(TRAF6)-nuclear factorκB(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 Gro

关 键 词：肿瘤坏死因子受体相关因子6-核因子κB信号通路 胆源性胰腺炎 氧化应激 基质金属蛋白酶 

分 类 号：R73[医药卫生—肿瘤]