逍遥散及其功效拆方对慢性铁过载诱导的大鼠肝脏铁死亡的影响  

Effects of Xiaoyao Powder and its Disassembled Prescriptions on Liver Iron Death Induced by Chronic Iron Overload in Rats

作　　者：邾莹莹 曹梦醒 周薏 阙任烨 李勇[1] ZHU Yingying;CAO Mengxing;ZHOU Yi(Department of Spleen and Stomach Department,Shanghai Municipal Hospital of Traditional Chinese Medicine(TCM),Shanghai University of TCM,Shanghai 200071,China)

机构地区：[1]上海中医药大学附属市中医医院脾胃科,200071 [2]上海中医药大学附属市中医医院消化科,200071 [3]上海中医药大学附属上海市中西医结合医院消化科,200082

出　　处：《医学研究杂志》2024年第10期52-59,共8页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81573775);上海市青年科技英才杨帆计划项目(19YF1445200);上海市卫生健康委员会中发办青年基金资助项目(2018LQ016);上海中医药大学项目(18LK074)。

摘　　要：目的通过右旋糖酐铁诱导大鼠肝脏铁过载,观察逍遥散对肝细胞铁死亡的影响及机制,并通过各功效拆方探索逍遥散中疏肝、养血、健脾功效在全方中的作用和地位。方法使用右旋糖酐铁连续7周腹腔注射,制作慢性铁过载诱导的大鼠肝脏铁死亡模型。在造模3周后开始药物干预,分别使用逍遥散全方、逍遥散去疏肝药、逍遥散去健脾药、逍遥散去养血药干预,另外使用去铁胺作为阳性对照药物。检测还原型谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)、亚铁离子、脂质过氧化活性氧(reactive oxygen species,ROS)的含量,通过RT-PCR及Western blot法检测大鼠肝组织BMP6/HJV/SMAD4及下游hepcidin-ferroportin轴基因或蛋白表达情况。结果模型组大鼠肝脏Fe^(2+)、MDA、ROS含量较对照组均显著升高,GSH含量显著下降,谷胱甘肽过氧化物酶4(Gpx4)、膜铁转运蛋白(ferroportin)mRNA表达显著下降,前列腺素内过氧化物合酶2(Ptgs2)、铁调素(hepcidin)mRNA及BMP6、HJV、SMAD4蛋白表达显著升高。相较于模型组,逍遥散全方及各功效拆方组、阳性对照组均可显著逆转上述指标。与逍遥散全方比较,逍遥散各功效拆方组在逆转上述指标的效果上均有显著降低(除逍遥散去健脾药在SMAD4蛋白表达方面与整方组比较,差异无统计学意义)。结论逍遥散可抑制右旋糖酐铁诱导大鼠肝脏铁死亡,可能与调控BMP6/HJV/SMAD4通路及其下游hepcidin-ferroportin轴相关,而逍遥散各功效拆方均对其抑制肝细胞铁死亡的过程起到了作用。Objective To induce iron overload in the liver of rats by iron dextran,observe the effect and mechanism of Xiaoyao Powder on liver cell iron death,and explore the role and position of Xiaoyao Powder′s liver soothing,blood nourishing,and spleen strengthening effects in the entire formula through the analysis of various functional formulas.Methods A rat liver iron death model induced by chronic iron overload was established by intraperitoneal injection of iron dextran for 7 consecutive weeks.After three weeks of modeling,drug intervention was initiated,using Xiaoyaosan Quanfang,Xiaoyaosan Qushugan Yao,Xiaoyaosan Jianpi Yao,and Xiaoyaosan Quxueyuan Yao respectively.In addition,deferoxamine was used as a positive control drug.Detect the content of reduced glutathione(GSH),malondialdehyde(MDA),ferrous ions,and lipid peroxidation ROS.RT-PCR and Western blot were used to detect the expression of BMP6/HJV/SMAD4 and downstream hepcidin ferroportin axis genes or proteins in rat liver tissue.Results The liver Fe^(2+),MDA and ROS contents of the model group rats were significantly increased compared to the control group,while the GSH content was significantly decreased.The mRNA expression of glutathione peroxidase 4(Gpx4)and membrane iron transporter(Fpn1)was significantly decreased,while the mRNA expression of prostaglandin peroxidase 2(Ptgs2)and hemodulin,as well as BMP6,HJV,and SMAD4 proteins,were significantly increased.Compared with the model group,the entire formula of Xiaoyaosan,as well as the various functional decoctions and positive control groups,can significantly reverse the above indicators.Compared with the whole formula of Xiaoyaosan,the efficacy of Xiaoyaosan in each disassembled formula group was significantly reduced in reversing the above indicators(except for the Xiaoyaosan spleen tonifying drug,which had no significant difference in SMAD4 protein expression compared to the whole formula group).Conclusion Xiaoyaosan can inhibit iron-induced liver ferroptosis in rats,which may be related to the regulatio

关 键 词：逍遥散 铁过载 铁死亡 肝纤维化 

分 类 号：R256.4[医药卫生—中医内科学]