The mRNA expression of Ntcp and Bsep in hepatic injury induced by lipopolysaccharide in mice / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effects of lipopolysaccharide (LPS) on the expressions of sodium taurocholate co-transporting polypeptide (Ntcp) and bile salt export pump (Bsep),as well as the liver function markers in the serum including total bilirubin (TBIL),total bile acids (TBA),alanine aminotransferase (ALT),aspartate aminotransferase (AST) in mice.Methods One hundred and twenty-eight C57BL/6 mice were intra-peritoneally injected with different doses of 5,10,20 or 40 mg/kg LPS (n =24),respectively.No treatment or treated with 0.9％ NaC1 in mice as controls.Serum TBIL,TBA,ALT and AST levels were measured at 24 h,48 h and 72 h after LPS injection in each group.The mRNA expressions of Ntcp and Bsep were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR).The liver histological sections were stained with haematoxylin and eosin (H&E).Results The Ntcp and Bsep mRNA expressions in mice liver were significantly lower in livers of LPS-treated mice within 24-72 h compared with control group,and the lowest level was reached at 24 h in a dose-dependent manner.And the relative expressions of Ntcp mRNA and Bsep mRNA were (0.64 ± 0.02),(0.53 ± 0.14),(0.25±0.09),(0.15±0.07)and (0.74±0.12),(0.58±0.11),(0.41±0.09),(0.27 ± ± 0.11) in livers of mice injected with LPS in the different doses of 5,10,20,40 mg/kg,respectively.In addition,serum levels of TBIL,TBA,ALT,and AST were significantly increased in mice of LPS-treated group compared with control group,particularly within 24 h after LPS treatment.Serum levels of TBIL,TBA,ALT,and AST were significantly decreased in mice of 40 mg/kg LPS-treated 72 h group compared with 24 h group presenting them with (1.29 ± 0.25) μ mol/L vs.(1.71 ± 0.22) μ moL/L,(6.97 ± 0.98) μmol/Lvs.(8.96±1.01) μmol/L,(120.17±21.08) U/L vs.(179.22±16.57) U/L,(360.34 ±35.31) U/L vs.(510.97 ± 34.70) U/L,respectively.Furthermore,histological changes in liver depend on dose and the course of LPS treatment.Cytoplasm rarefaction and inflammatory cells infiltration were detected at 24 h after treatment with 5 or 10 mg/kg LPS.Acidophilic and vacuolar degeneration,neutrophils infiltration in the hepatic sinusoid and portal area,the proliferation of bile ductulus were observed at 48 h,72 h after treatment with 5 or 10 mg/kg LPS.In the 20 or 40 mg/kg LPS treatment groups,focal necrosis,infiltration with inflammatory cells,proliferation of bile ductulus and expansion of duct were observed at 24 h,48 h and 72 h after LPS treatment.Conclusions LPS decreases the mRNA expressions of Ntcp and Bsep in a dose dependent manner in mice,contributing to mechanism of liver injury induced by endotoxin.