大黄素调控FGF19/FGFR4通路抑制肝星状细胞活化的抗肝纤维化机制研究  

Study on the anti fibrotic mechanism of emodin in inhibiting hepatic stellate cell activation by regulating the FGF19/FGFR4 pathway

作　　者：汤琴 陶茹 赵彤芳[2] 叶宇婕 TANG Qin;TAO Ru;ZHAO Tongfang;YE Yujie(Department of Hepatology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203;GCP Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,China)

机构地区：[1]上海中医药大学附属曙光医院肝病科,上海201203 [2]上海中医药大学附属曙光医院GCP中心

出　　处：《胃肠病学和肝病学杂志》2024年第10期1286-1290,共5页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的探究大黄素调控FGF19/FGFR4通路抑制肝星状细胞(hepatic stellate cell,HSC)活化的抗肝纤维化机制。方法体外培养人HSC细胞株LX-2细胞,将LX-2细胞分为对照组、大黄素低剂量组、大黄素高剂量组、H3B-6527组(FGF19/FGFR4信号通路抑制剂)、大黄素高剂量+oe-NC组、大黄素高剂量组+oe-FGFR4组。CCK-8检测细胞增殖,流式细胞术检测细胞凋亡,qRT-PCR实验检测细胞FGF19和FGFR4基因表达;Western blotting检测Col-Ⅰ、Col-Ⅲ、α-SMA、Bcl-2、Bax、FGF19、FGFR4蛋白水平。结果与对照组相比,大黄素低、高剂量组和H3B-6527组LX-2细胞OD 450(24 h、48 h)值、FGF19 mRNA、FGFR4 mRNA表达、Col-Ⅰ、Col-Ⅲ、α-SMA、Bcl-2、FGF19、FGFR4蛋白表达显著降低,凋亡率和Bax蛋白表达显著升高(P<0.05);与大黄素高剂量组相比,H3B-6527组LX-2细胞各项检测指标差异无统计学意义(P>0.05);过表达FGFR4减弱了大黄素对LX-2细胞行为及以上蛋白表达的影响。结论大黄素通过抑制FGF19/FGFR4通路可抑制HSC的生物学活性进而实现抗肝纤维化的作用。Objective To investigate the anti fibrotic mechanism of emodin in inhibiting hepatic stellate cell(HSC)activation by regulating the FGF19/FGFR4 pathway.Methods Human HSC cell line LX-2 cells were cultured in vitro and grouped into control group,low-dose emodin group,high-dose emodin group,H3B-6527 group(FGF19/FGFR4 signaling pathway inhibitor),high-dose emodin+oe-NC group and high-dose emodin+oe-FGFR4 group.CCK-8 was applied to detect cell proliferation;flow cytometry was applied to detect cell apoptosis;qRT-PCR experiment was applied to detect the expression of FGF19 and FGFR4 genes in cells.Western blotting was applied to detect the levels of Col-Ⅰ,Col-Ⅲ,α-SMA,Bcl-2,Bax,FGF19 and FGFR4 proteins.Results Compared with the control group,the OD 450(24 h,48 h)value,FGF19 mRNA,FGFR4 mRNA expression,Col-Ⅰ,Col-Ⅲ,α-SMA,Bcl-2,FGF19,FGFR4 protein expression in LX-2 cells in low-dose and high-dose emodin groups and H3B-6527 group were obviously reduced,and the apoptosis rate and Bax protein expression were obviously increased(P<0.05).Compared with the high-dose emodin group,there was no statistically obvious difference in various detection indicators of LX-2 cells in the H3B-6527 group(P>0.05).Overexpression of FGFR4 weakened the effects of emodin on the behavior of LX-2 cells and protein expression.Conclusion Emodin can inhibit the biological activity of HSC and achieve anti liver fibrosis effects by inhibiting the FGF19/FGFR4 pathway.

关 键 词：大黄素 FGF19/FGFR4通路 肝星状细胞 肝纤维化 

分 类 号：R575[医药卫生—消化系统]