中国药房2017,Vol.28Issue(19):2620-2624,5.DOI:10.6039/j.issn.1001-0408.2017.19.08
卡维地洛对瘦素诱导的人肝星状细胞活化增殖的影响及机制研究
Study on the Effect and Its Mechanism of Carvedilol on Leptin-induced Activation and Proliferation of Hu-man Hepatic Stellate Cells
摘要
Abstract
OBJECTIVE:To study the effect and its mechanism of carvedilol on leptin-induced activation and proliferation of LX2 human hepatic stellate cells(HSC-LX2). METHODS:HSC-LX2 with logarithmic growth periods were divided into blank con-trol group,leptin-stimulated group and carvedilol low-concentration,medium-concentration,high-concentration groups(5,10,20μmol/L). Except for the blank control group,other groups were added 0.1 g/L leptin and corresponding concentration of carvedilol. After 24 h,MTT method was used to detect the optical density(OD)value of cells and calculate the proliferation rate. Flow cytom-etry was used to detect the cell cycle and apoptosis. Real-time fluorescence quantitative polymerase chain reaction method was used to detect the α-smooth muscle actin (α-SMA),matrix metalloproteinase inhibition factor 1 (TIMP-1),leptin,leptin receptor mRNA expressions. Western blot method was used to detect phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal trans-duction and transcriptional activator 3 (p-STAT3) protein expressions. RESULTS:Compared with blank control group,OD value of cell was increased in leptin-stimulated group;apoptotic rate was decreased;cells of G0/G1 were decreased;α-SMA,TIMP-1, leptin,leptin receptor mRNA expressions and p-JAK2,p-STAT3 protein expressions were increased (P<0.05). Compared with leptin-stimulated group,OD values of cells were decreased in carvedilol concentration groups;apoptotic rate was increased,and the cells were mainly blocked in G0/G1 phase;α-SMA,TIMP-1,leptin,leptin receptor mRNA expressions and p-JAK2,p-STAT3 protein expressions were decreased(P<0.05)and was concentration-depended(P<0.05). CONCLUSIONS:Carvedilol can inhibit the activation and proliferation of leptin-induced HSC-LX2,promote its apoptosis. The mechanism may associate with down-regulat-ing leptin,leptin receptor gene expression and blocking JAK2/STAT3 signal pathway activation by leptin in cells.关键词
卡维地洛/人肝星状细胞/增殖/凋亡/瘦素/Janus激酶2/信号转导和转录激活因子3Key words
Carvedilol/Human hepatic stellate cells/Proliferation/Apoptosis/Leptin/Janus kinase 2/Signal transduction and transcriptional activator 3分类
医药卫生引用本文复制引用
穆华,张哲,梁传栋,刘娜..卡维地洛对瘦素诱导的人肝星状细胞活化增殖的影响及机制研究[J].中国药房,2017,28(19):2620-2624,5.基金项目
河北省医学科学研究重点课题计划项目(No. ZL20140250) (No. ZL20140250)