双氢青蒿素对不同铁负载条件下肝星状细胞活化的影响  

Impact of Dihydroartemisinin on Hepatic Stellate Cell Activation under Different Iron loading Conditions

作　　者：江远[1] 张玲[1] 何金洋[2] 

机构地区：[1]广州医科大学附属深圳沙井医院 [2]广州中医药大学热带医学研究所

出　　处：《中医杂志》2017年第10期873-877,共5页Journal of Traditional Chinese Medicine

基　　金：广东省中医药局建设中医药强省项目(20152066)

摘　　要：目的探讨双氢青蒿素体外抗肝纤维化作用及其可能机制。方法双氢青蒿素设50、25、12.5、6.25、3.125、1.5625、0.78125、0.390125μg/ml共8个浓度进行细胞毒性试验,选择最大无细胞毒作用的双氢青蒿素浓度进行以下实验。体外培养肝星状细胞(HSC),分为正常对照组、铁沉积模型组[25μmol/L柠檬酸铁胺(FAC)]、去铁铵组(50μmol/L去铁铵)、双氢青蒿素组(双氢青蒿素)、铁沉积+双氢青蒿素组(25μmol/L FAC+双氢青蒿素)和去铁铵+双氢青蒿素组(50μmol/L去铁铵+双氢青蒿素),培养24 h。免疫组化法检测各组细胞中α平滑肌肌动蛋白(α-SMA)的表达,PCR法检测HSC铁代谢及细胞活化相关因子[包括铁调素、转铁蛋白受体1(TfR1)、Ⅰ型胶原及转化生长因子β1(TGF-β1)]mRNA表达。结果筛选出6.25μg/ml浓度的双氢青蒿素进行试验。铁沉积模型组细胞中α-SMA大量表达,各给药组细胞中α-SMA表达较正常对照组和铁沉积模型组明显减少。铁沉积模型组铁调素mRNA表达明显降低,而经去铁铵和(或)双氢青蒿素干预后,铁调素mRNA表达均显著升高(P<0.05)。双氢青蒿素组、铁沉积+双氢青蒿素组和去铁铵+双氢青蒿素组能明显降低TfR1、Ⅰ型胶原、TGF-β1 mRNA表达(P<0.05)。结论双氢青蒿素具有一定的体外抗肝纤维化作用,其机制与调节细胞铁的代谢、抑制肝星状细胞活化有关。Objective To explore the anti hepatic fibrosis effect of dihydroartemisinin in vitro and the possible mechanism. Methods Eight concentration of dihydroartemisinin（50,25,12. 5,6. 25,3. 125,1. 5625,0. 78125 and 0. 390125 μg/ml） were designed to make cytotoxicity test. The largest concentration of dihydroartemisinin without cytotoxicity was chosen for the following tests. Hepatic stellate cells were cultured in vitro,which were divided into the normal control group,the iron deposition model group [25 μmol/L ferric ammonium citrate（FAC） ],the deferoxamine group（50 μmol/L deferoxamine）,the dihydroartemisinin group（dihydroartemisinin）,the iron deposition ＋dihydroartemisinin group（25 μmol/L FAC ＋ dihydroartemisinin） and the deferoxamine ＋ dihydroartemisinin group（50 μmol/L deferoxamine ＋ dihydroartemisinin）. All cells were cultured for 24 h. The expressions of cells＇ αsmooth muscle actin（α-SMA） in all groups were detected with immunohistochemical method. The iron metabolism and the mRNA expressions of cell activation correlation factors [including hepcidin,transferrin receptor 1（TfR1）,and collagen I and Transforming Growth Factor β1（TGF-β1） ]were detected with polymerase chain reaction（PCR） method.Results Dihydroartemisinin with the concentration of 6. 25 μg/ml was chosen to be tested. There were a lot of cells＇ α-SMA expressions in the iron deposition model group. Cells＇ α-SMA expressions in the medicine groups were less than those in the normal control group and the iron deposition model group. Hepcidin mRNA expressions in the iron deposition model group decreased,while after being intervented with deferoxamine and/or dihydroartemisinin,hepcidin mRNA expressions increased（P〈0. 05）. The mRNA expressions of TfR 1,as well as collagen I and TGF-β1decreased in the dihydroartemisinin group,the FAC ＋ dihydroartemisinin group and the deferoxamine ＋ dihydroartemisinin group. Conclusion Dihydroartemisinin might have anti hepatic fibrosis effect in vitr

关 键 词：肝纤维化 双氢青蒿素 铁代谢 肝星状细胞 细胞活化 

分 类 号：R285[医药卫生—中药学]