白藜芦醇对胆道梗阻再通大鼠肝损害的保护机制-安徽医药杂志.docVIP

白藜芦醇对胆道梗阻再通大鼠肝功能的保护作用 许朝龙 邬善敏 苗志钊 赵凯亮 陈飞 范迪欢 作者单位：430060 武汉大学人民医院肝胆腔镜外科 通信作者：邬善敏，男，教授，硕士生导师，主要从事肝胆外科基础与临床研究，Email163.com 摘要 目的 研究白藜芦醇（Res）对胆道梗阻再通大鼠肝损害的保护作用及机制。方法 雄性Wistar大鼠60只，随机分为4组，即A组:假手术组，B组：梗阻性黄疸模型组，C组：梗阻性黄疸模型＋胆道再通组，D组:梗阻性黄疸＋胆道再通 +Res干预组。连续给药7d,实验结束后检测各组大鼠血清中总胆红素（TBIL）、直接胆红素(DBIL)、丙氨酸氨基转氨酶（ALT）mRNA的表达，Western blot检测肝组织SIRT1蛋白和核因子-κB（NF-κB）α（PPARα）蛋白在肝脏中的表达，原位末端标记（TUNEL）法检测肝细胞凋亡。结果 与假手术组比较，模型组血清ALT水平升高，SIRT1 mRNA及蛋白、PPARα蛋白表达降低，NF-κB蛋白表达升高，细胞凋亡率升高（P0.05）；而造模后胆道再通组与模型组比较，血清ALT水平降低，SIRT1 mRNA及蛋白、PPARα蛋白表达增加，NF-κBp蛋白表达降低，细胞凋亡率降低（P0.05）；白藜芦醇组与C组比较：血清ALT水平降低，SIRT1 mRNA及蛋白、PPARα蛋白表达增加，NF-κBp蛋白表达降低，细胞凋亡率降低（P0.05）。结论 Res可能通过激活SIRT1抑制NF-κB，发挥抗炎、抗凋亡作用，通过促进PPARα的表达发挥抗氧化作用，从而减轻胆道梗阻再通大鼠的肝损害，促进肝功能恢复。 关键词 白藜芦醇；梗阻性黄疸；再通；沉默信息调控因子；过氧化物酶体增殖物剂激活受体α；核因子-κB Protective effect of the resveratrol on liver injury in rats after recanalization of biliary obstruction Xu Chaolong,Wu Shanmin,Miao Zhizhao,Zhao Kailiang,Chen Fei,Fan dihuan Department of Hepatobiliary Surgery,Renmin Hospital of Wuhan University,Wuhan430060,China Corresponding author：Wu Shanmin,Email163.com Abstract Objective To explore the protective effect of the resveratrol(Res) on liver injury in rats after recanalization of biliary obstruction.Methods Sixty healthy male Wistar rats were divided randomly into four groups,group A:sham group,group B:obstructive jaundice one week group,group C:obstructive jaundice one week and recanalization one week+NS group,group D:obstructive jaundice one week and recanalization one week+Res group.The levels of total bilirubin(TBIL),direct bilirubin(DBIL) and serum alanine aminotransferase(ALT) were measured.Real-time polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of silent information regulator 1(SIRT1).The expression of the SIRT1 and nuclear factor-κB (NF-κB) proteins were detected by western blot.Immunocytochemical assay was performed to examine peroxisome proliferator activated receptor-alpha (PPARα) protein.Hepatocellu