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

发布时间：2018-06-05 06:23

本文选题：卡维地洛 + 人肝星状细胞　；参考：《中国药房》2017年19期

【摘要】：目的:研究卡维地洛对瘦素诱导的LX2人肝星状细胞(HSC-LX2)活化增殖的影响及机制。方法:取对数生长期的HSC-LX2细胞分为空白对照组、瘦素刺激组和卡维地洛低、中、高浓度组(5、10、20μmol/L),除空白对照组外,其余各组均加入0.1 g/L的瘦素及相应浓度的卡维地洛作用24 h。采用MTT法检测细胞的光密度(OD)值,计算细胞增殖抑制率;流式细胞术检测细胞周期和凋亡情况;实时荧光定量聚合酶链式反应法检测细胞中α-平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶抑制因子1(TIMP-1)、瘦素及瘦素受体m RNA表达;Western blot法检测磷酸化Janus激酶2(p-JAK2)、磷酸化信号转导和转录激活因子3(p-STAT3)蛋白表达。结果:与空白对照组比较,瘦素刺激组细胞的OD值增加、凋亡率降低、G_0/G_1期细胞减少(P0.05);α-SMA、TIMP-1、瘦素、瘦素受体m RNA表达和p-JAK2、p-STAT3蛋白表达均增强(P0.05)。与瘦素刺激组比较,卡维地洛各浓度组细胞的OD值减小、凋亡率升高、细胞主要阻滞在G_0/G_1期(P0.05);α-SMA、TIMP-1、瘦素、瘦素受体m RNA表达和p-JAK2、p-STAT3蛋白表达均减弱(P0.05),且呈浓度依赖性(P0.05)。结论:卡维地洛能够抑制瘦素诱导的HSC-LX2细胞的活化增殖,促进HSC-LX2细胞凋亡;其机制可能与下调瘦素、瘦素受体基因表达并阻断瘦素诱导的细胞内JAK2/STAT3信号通路激活有关。
[Abstract]:Objective: To study the effect and mechanism of carvedilol on the activation and proliferation of LX2 human hepatic stellate cells (HSC-LX2) induced by leptin. Methods: the HSC-LX2 cells from the logarithmic growth period were divided into blank control group, leptin stimulation group and carvedilol low, medium and high concentration group (5,10,20 mu mol/L), except for the blank control group, all the other groups were added to 0.1 g/L leptin and phase. The concentration of carvedilol at 24 h. was used to detect cell light density (OD) and cell proliferation inhibition rate; cell cycle and apoptosis were measured by flow cytometry; alpha smooth muscle actin (alpha -SMA), matrix metalloproteinase inhibitor 1 (TIMP-1), leptin and leptin were detected by real-time fluorescence quantitative polymerase chain reaction. The expression of leptin receptor m RNA; Western blot method to detect the phosphorylated Janus kinase 2 (p-JAK2), phosphorylation signal transduction and transcription activator 3 (p-STAT3) protein expression. Results: compared with the blank control group, the OD value of the cells in the leptin stimulation group increased, the apoptosis rate decreased and the G_0/G_1 phase cell decreased (P0.05); alpha -SMA, TIMP-1, leptin, leptin receptor M And p-JAK2, the expression of p-STAT3 protein increased (P0.05). Compared with the leptin stimulation group, the OD value of cells in the concentration group of carvilol decreased, the apoptosis rate increased, and the cells mainly blocked in the G_0/G_1 phase (P0.05); alpha -SMA, TIMP-1, leptin, m RNA expression of M, p-JAK2, p-STAT3 protein decreased (P0.05), and showed concentration dependence. Carvedilol can inhibit the activation and proliferation of leptin induced HSC-LX2 cells and promote apoptosis of HSC-LX2 cells. The mechanism may be related to the downregulation of leptin, leptin receptor gene expression and blocking the activation of JAK2/STAT3 signaling pathway induced by leptin.
【作者单位】：河北省人民医院门诊办公室;河北省人民医院代谢病重点实验点;河北省人民医院神经外二科;河北省人民医院消化内二科;
【基金】：河北省医学科学研究重点课题计划项目(No.ZL20140250)
【分类号】：R96

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