首页|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

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

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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 OD450(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.
Study on the anti fibrotic mechanism of emodin in inhibiting hepatic stellate cell activation by regulating the FGF19/FGFR4 pathway
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 ap-plied 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 OD450(24 h,48 h)value,FGF19 mRNA,FGFR4 mRNA expression,Col-Ⅰ,Col-Ⅲ,α-SMA,Bcl-2,FGF19,FGFR4 pro-tein 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 in-hibiting the FGF19/FGFR4 pathway.

EmodinFGF19/FGFR4 pathwayHepatic stellate cellsHepatic fibrosis

汤琴、陶茹、赵彤芳、叶宇婕

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上海中医药大学附属曙光医院肝病科,上海 201203

上海中医药大学附属曙光医院 GCP 中心

大黄素 FGF19/FGFR4通路 肝星状细胞 肝纤维化

2024

胃肠病学和肝病学杂志
郑州大学

胃肠病学和肝病学杂志

CSTPCD
影响因子:1.029
ISSN:1006-5709
年,卷(期):2024.33(10)
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