Effcet Of Isoniazid And Rifampicin On Expression Of Bile Acid Transporters Ntcp And Bsep In Mice

Objective:To study the effect of isoniazid and rifampicin on expression of bile acid-related transporter Ntcp, Bsep expression in a mouse model of isoniazid (INH) and rifampicin (RFP) alone or in combination induced liver injury and discuss whether aggravated liver injury caused by rifampicin and isoniazid were related to changes expression of these transporters. Methods: Fifty-six female ICR mouse (29.8+1.4g) were divided into seven groups(low-dose and high dose groups), low-dose group were intragastric administrated every day with50mg/kg INH,100mg/kg RFP,50mg/kg INH+100mg/kg RFP, high dose group were administrated with100mg/kg INH,200mg/kg RFP,100mg/kg INH+200mg/kg RFP, respectively, control group was given dissolvent (0.2%CMC-Na),for14consecutive days. Recording food surplus, growth and appetite, the colour, urine and response to external stimulus of experiment mouse in each group the next day after administration. On the15th day the mice were anesthetized with chloral hydrate, the concentration of the serum biochemical index were measured by extracting the eyeball blood,liver tissue specimens from each group were fixed in10%formalin for pathologic sections, HE staining; another tissue were fixed in4%paraformalde-hyde to quantitate the expression of transporters by immunehistochemical; and the rest were cryopreserved at-70℃to determine the expression of Ntcp and of Bsep using Western blot. Results:Related indicators in each experimental group of liver injury model in mice exhibit a significant change, biochemical markers ALT, AST, TBil, DBil, ALP, TBA, MDA were significantly changed in high dose experiment groups, the results of liver morphology and pathology showed liver damage low dose groups had a little change.Ntcp、Bsep protein expressed in both control group and experiment groups. Expression of Ntcp and Bsep was down-regulated in low and high dose groups compared with control group, and their expression were significantly down-regulated in H-INH+RFP group (.P<0.05),and the result show a negative correlation between the expression of Ntcp and Bsep and serum Bile acid secretion (P<0.05) Conclusion:Both high dose of INH、RFP and their combination can induce liver injury in mouse and down-regulated the expression of bile-acid related transporter Ntcp and Bsep. In addition, the serum biochemical indexes and histopathological changes obviously lagged behind the significant expression change of the transporters. Liver damage caused by INH、RFP pathology is the the result of combined action of transporter and change of endogenous substances (bilirubin, bile acid, etc.)...