Study on the Effect and Its Mechanism of Carvedilol on Leptin-induced Activation and Proliferation of Hu-man Hepatic Stellate Cells
10.6039/j.issn.1001-0408.2017.19.08
- VernacularTitle: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
- Author:
Hua MU
;
Zhe ZHANG
;
Chuandong LIANG
;
Na LIU
- Keywords:
Carvedilol;
Human hepatic stellate cells;
Proliferation;
Apoptosis;
Leptin;
Janus kinase 2;
Signal transduction and transcriptional activator 3
- From:
China Pharmacy
2017;28(19):2620-2624
- CountryChina
- Language:Chinese
-
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.
