目的 研究肝豆灵对Wilson病(Wilson's disease,WD)大鼠肝组织miRNA-122表达的影响,探究其保护肝脏的机制.方法 将24只Wistar大鼠随机分为空白对照组、模型组、青霉胺组和肝豆灵组.铜负荷喂养8周后,分别用青霉胺、肝豆灵以成人等效剂量灌胃,空白对照组及模型组均以等量生理盐水灌胃,每组均灌胃4周.观察各组大鼠肝功能及肝组织miRNA-122的表达水平.结果 肝豆灵和青霉胺均可显著降低WD大鼠异常升高的血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBil)(P<0.05,或P<0.01),显著升高WD大鼠肝组织异常降低的miRNA-122表达水平(P<0.01).肝豆灵降低血清ALT、AST和TBil的作用及升高肝组织miRNA 122表达的作用显著优于青霉胺(P<0.05,或P<0.01).结论 肝豆灵保护WD大鼠肝功能的作用与其上调肝组织miRNA-122的表达有关.
Objective To study the effect of Gandouling on the miRNA-122 expression in liver tissues of rats with Wilson's disease (WD) and to explore the action mechanism of Gandouling in liver protection.Methods Twenty-four Wistar rats were randomly divided into blank control group,model group,penicillamine group,and Gandouling group.All rats except those in the blank control group were given copper-overloaded diets for 8 weeks.Then,the penicillamine group and Gandouling group received penicillamine and Gandouling,respectively,by gavage at human-equivalent doses,while the blank control group and model group received an equal volume of normal saline by gavage; intragastric administration was performed for 4 weeks in each group.The liver function and hepatic miRNA-122 expression in each group were measured.Results Both Gandouling and penicillamine significantly reduced the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),and total bilirubin (TBil) (P<0.05 or P<0.01),which were abnormally elevated in rats with WD,and significantly increased miRNA-122 expression (P<0.01),which was significantly reduced in the liver tissues of rats with WD.Gandouling was significantly superior to penicillamine in reducing serum ALT,AST,and TBil levels and increasing hepatic miRNA-122 expression (P<0.05 or P<0.01).Conclusion Gandouling can protect the liver function of rats with WD,possibly by increasing hepatic miRNA-122 expression.