异烟肼通过改变肝脏转运体NTCP和BSEP的表达诱导HepG2细胞损伤

Isoniazid induced injury in HepG2 cells by altering expression of liver transporter NTCP and BSEP

目的:基于Na^+-牛磺胆酸共转运多肽(NTCP)和胆盐输出泵(BSEP)探讨异烟肼(INH)致HepG2细胞损伤的机制。方法:不同浓度异烟肼作用于细胞后:(1)MTT法检测细胞存活率;(2)测定细胞内总胆汁酸(TBA)浓度;(3)Western-blot检测NTCP和BSEP蛋白表达的变化。结果:(1)HepG2细胞存活率随着异烟肼浓度升高而呈剂量依赖性的降低。(2)异烟肼可使细胞内胆汁酸浓度明显升高。(3)异烟肼浓度为6.5,13,26 mmol·L^(-1)时上调了NTCP的表达;异烟肼浓度为52,104 mmol·L^(-1)时使NTCP表达回到正常水平。(4)异烟肼浓度为104 mmol·L^(-1)时明显抑制了BSEP的表达。结论:异烟肼可引起HepG2细胞内胆汁酸升高和细胞毒性,其机制可能与调控NTCP和BSEP的表达有关。

OBJECTIVE To study mechanisms of isoniazid（INH）induced HepG2 cell injury based on Na＋-taurcholate cotransporting polypeptide（NTCP）and bile salt export pump（BSEP）.METHODS Adding INH to HepG2 cells at different concentrations：MTT was used to test cell vibility;biochemical analysis was used to test total bile acids（TBA）concentration;Western Blot was used to test protein expressions of NTCP and BSEP.RESULTS Cell viability decreased in a concentration dependent manner.INH increased TBA concentration in HepG2 cells.Protein expression of NTCP increased at INH concentrations of 6.5,13 and 26 mmol·L^（-1）,and went back to normal level at INH concentrations of 52 and 104 mmol·L^（-1）.BSEP protein expression decreased at the INH concentration of 104 mmol L^（-1）.CONCLUSION INH induces increased TBA concentration and cytotoxicity in HepG2 cells,which may be correlated with NTCP adjustment and BSEP expression.