黛矾散干预JAK2/STAT3/SOCS3信号通路保护原发性胆汁性胆管炎小鼠模型肝内胆管的研究OA
Study on Daifan Powder Intervening JAK2/STAT3/SOCS3 Signaling Pathway to Protect Intrahepatic Bile Ducts in Mouse Models of Primary Biliary Cholangitis
目的 观察黛矾散调控JAK2/STAT3/SOCS3信号通路对原发性胆汁性胆管炎(PBC)免疫炎症反应的保护作用并探讨其机制.方法 将C57BL/6J小鼠分为对照组、模型组、熊去氧胆酸组(100 mg/kg)和黛矾散低、中、高剂量组(90、180、360 mg/kg),制备原发性胆汁性胆管炎后连续灌胃给药28 d.测定小鼠肝脏指数;全自动生化分析仪检测血清γ-谷氨酰转移酶(γ-GT)、总胆汁酸(TBA)、总胆红素(TBil)、谷草转氨酶(AST)、谷丙转氨酶(ALT)含量;苏木精-伊红(HE)染色和马松(Masson)染色观察肝组织病理学改变;酶联免疫吸附法(ELISA)检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)含量;反转录聚合酶链反应(RT-PCR)检测 JAK2、STAT3、SOCS3 mRNA水平;蛋白质印迹法(Western blotting)检测 JAK2、p-JAK2、STAT3、p-STAT3、SOCS3水平.结果 与对照组相比,模型组肝指数升高(P＜0.01);γ-GT、TBA、TBil、AST、ALT升高(P＜0.01);肝组织门管区多发炎症细胞聚集,伴见大量胶原纤维沉积;TNF-α、IL-6、IL-1β表达上调(P＜0.01);肝组织 p-JAK2/JAK2、p-STAT3/STAT3 蛋白比值及 JAK2、STAT3 mRNA 相对表达上调(P＜0.01),SOCS3蛋白及mRNA相对表达下调(P＜0.01).与模型组相比,各给药组上述指标明显改善(P＜0.05或P＜0.01),肝组织门管区炎症及胶原纤维沉积减轻.结论 黛矾散抑制PBC小鼠肝内胆管损伤可能与JAK2/STAT3/SOCS3信号通路介导的炎症反应相关.
Objective:To investigate the effect and mechanism of Daifan Powder in regulating JAK2/STAT3/SOCS3 signaling pathway on immune inflammatory response in primary biliary cholangitis(PBC).Methods:C57BL/6J mice were divided into the control group,model group,ursodeoxycholic acid group(100 mg/kg),and low-,medium-,and high-dose Daifan Powder groups(90,180,360 mg/kg).After preparing model of primary bili-ary cholangitis,all mice were given intragastric administration continuously for 28 days.Liver index of mice was measured;the levels of biochemical indicators including γ-GT,TBA,TBil,AST and ALT were detected by automat-ic biochemical analyzer;hematoxylin-eosin(HE)staining and Masson staining were used to observe histopathologi-cal changes of liver;the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1 β(IL-1β)were detected by enzyme-linked immunosorbent assay(ELISA);the mRNA levels of JAK2,STAT3 and SOCS3 were detected by reverse transcription-polymerase chain reaction(RT-PCR);the levels of JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were detected by Western blotting.Results:Compared with the control group,the liver index in the model group was significantly increased(P＜0.01);γ-GT,TBA,TBil,AST,ALT were elevated(P＜0.01);massive inflammatory cell infiltration and collagen fiber deposition were observed in the portal area of liver tissue;the expressions of TNF-α,IL-6 and IL-1 β were up-regulated(P＜0.01);the protein ratios of p-JAK2/JAK2,p-STAT3/STAT3 and the relative mRNA expressions of JAK2 and STAT3 in liver tissue were up-regulated(P＜0.01),while the protein and mRNA expressions of SOCS3 were down-regulated(P＜0.01).Compared with the model group,the above indicators in each treatment group were significantly improved(P＜0.05 or P＜0.01),and inflammation and collagen deposition in the portal area of liver tissue were alleviated.Conclusion:Daifan Powder can alleviate intrahepatic bile duct injury in PBC mice,which may be related to the regulation of inflamma-tory response mediated by JAK2/STAT3/SOCS3 signaling pathway.
计洋;徐子皓;徐俊;程良斌
湖北中医药大学,湖北武汉 430065||湖北中医药大学附属湖北省中医院,湖北武汉 430061湖北中医药大学,湖北武汉 430065湖北中医药大学,湖北武汉 430065湖北中医药大学附属湖北省中医院,湖北武汉 430061
医药卫生
原发性胆汁性胆管炎黛矾散肝内胆管损伤JAK2/STAT3/SOCS3信号通路小鼠
Primary biliary cholangitisDaifan PowderIntrahepatic bile duct injuryJAK2/STAT3/SOCS3 sig-naling pathwayMice
《中国中医急症》 2026 (5)
516-520,536,6
国家自然科学基金面上项目(82274367)湖北省中医药管理局面上项目(ZY2025M007)湖北省时珍人才工程科研项目(鄂卫函[2024]256号)
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