中国临床药理学杂志2024，Vol.40Issue(12)：1759-1763,5.DOI:10.13699/j.cnki.1001-6821.2024.12.013
Licraside激活FXR缓解胆汁淤积的药理学研究
Pharmacological research of Licraside in activating FXR to relieve cholestasis
摘要
Abstract
Objective To investigate the molecular mechanism of action of isoglycoside-4'-O-apigenin(1 → 2)glucoside(licraside)intervention in alleviating cholestasis.Methods Farnesol X receptor(FXR)was silenced in human HepG2 cells using lentivirus,and bilirubin and α-isothiocyanate(ANIT)were used to induce HepG2 cells to construct a hypercholate-hyperbilirubin model.The effects of licraside on cell viability,biochemical indices contents and the expression level of FXR and its downstream related proteins in the model were investigated.HepG2 cells and FXR-silenced HepG2 cells were divided into normal,model and experimental groups.Bilirubin and probenecid were added to all groups except the normal group,and 80 μmol·L-1 licraside was added to the experimental group.After 24 h of culture,cell viability and the levels of total bile acids(TBA),bilirubin and other biochemical indices were examined in each group;the protein expression levels of FXR and bile salt efflux pump(BSEP)were examined in each group by Western blot assay.Results The cell viability in HepG2 cells normal group,HepG2 cells model group,HepG2 cells experimental group,siFXR-HepG2 cells normal group,siFXR-HepG2 cells model group and siFXR-HepG2 cells experimental group were(100.00±17.15)％,(39.41±2.91)％,(70.79±3.74)％,(81.41±5.12)％,(33.49±2.69)％and(44.08±4.82)％;the levels of TBA were(7.98±5.87),(46.18±10.93),(9.25±7.20),(11.18±3.36),(38.28±5.12)and(34.79±5.39)μmol·L-1;the levels of total bilirubin were(5.21±3.27),(40.29±24.88),(5.21±2.64),(12.00±4.64),(56.36±14.85)and(15.39±5.56)μmol·L-1;the relative expression levels of FXR protein were 1.00±0.10,0.81±0.07,1.11±0.09,0.10±0.02,0.12±0.02 and 0.10±0.04;the relative expression levels of BSEP protein were 1.00±0.17,0.81±0.02,0.88±0.03,0.70±0.09,0.49±0.07 and 0.60±0.10.The differences of the above indexes in the HepG2 cells experimental group compared with the model group were statistically significant(P＜0.001,P＜0.01);except for TBA,the differences of the above indexes in siFXR-HepG2 cells experimental group compared with the model group were statistically significant(P＜0.001,P＜0.01).Conclusion Licraside can effectively reduce the biochemical indices level of hypercholate-hyperbilirubin cell model.This effect is achieved by agonizing of FXR protein expression,increase the efflux of bile acid salt and then reduce the synthesis of bile acids,and eventually achieve the effect of alleviating the cholestasis.关键词
异甘草素-4'-O-芹糖(1→2)葡萄糖苷(licraside)/法尼醇X受体/激动药/胆汁淤积Key words
isoglycoside-4'-O-apigenin(1→2)glucoside/farnesol X receptor/agonist/cholestasis分类
医药卫生引用本文复制引用
王国旭,则巴努尔·约麦尔江,张慧雨,席莉莉,张帆,魏玉辉..Licraside激活FXR缓解胆汁淤积的药理学研究[J].中国临床药理学杂志,2024,40(12):1759-1763,5.基金项目
国家自然科学基金资助项目(81960646,82004080) （81960646,82004080）
兰州市科技局科技计划基金资助项目(2022-3-43) （2022-3-43）
