Objective To investigate the expression characteristics and significance of ABCB11( bile salt export pump,BSEP),ABCC2( multidrug resistant protein 2,MRP2),and ABCB4( multidrug resistance associated protein 3,MDR3) in the liver tissue in bile duct injury type of drug-induced liver injury( DILI). Methods Clinical data were collected from 112 patients who had a definite history of medication and were diagnosed with bile duct injury type of DILI based on liver biopsy in The Fifth Hospital of Shijiazhuang from January 2010 to June 2017. The patients were divided into mixed hepatitis group with 40 patients,cholestatic hepatitis group with 40 patients,and simple cholestasis group with 32 patients,and 20 hepatitis B virus carriers without cholestasis were enrolled as control group. Liver biopsy was performed for all subjects to perform immunohistochemical staining of BSEP,MDR3,and MRP2,and the expression characteristics of the three proteins and their association with pathomorphological changes were observed. The expression of these three transport proteins was compared between the three subtypes and its correlation with total bilirubin( TBil),direct bilirubin( DBil),alkaline phosphatase,gamma-glutamyl transpeptidase,and total bile acid( TBA) was analyzed. A one-way analysis of variance was used for comparison of continuous data between groups,and the least significant difference t-test was used for further comparison between two groups; a Pearson correlation analysis was performed to investigate correlation. Results Compared with the control group,the mixed hepatitis group,the cholestatic hepatitis group,and the simple cholestasis group had significant reductions in the expression of BSEP,MDR3,and MRP2 in liver tissue( F =48. 765,45. 424,and 77. 434,all P < 0. 05),and the comparison between any two groups showed that the cholestatic hepatitis group had significantly greater reductions than the mixed hepatitis group and the simple cholestasis group( all P < 0. 05). The degree of hepatocyte swelling and feather-like degeneration due to cholestasis increased with the reduction in the expression of BSEP,MRP2 and MDR3 in the area of cholestasis. In the cholestatic hepatitis group,BSEP was moderately negatively correlated with TBA( r =-0. 640,P = 0. 008),and in the simple cholestasis group,MRP2 was moderately negatively correlated with TBil( r =-0. 597,P = 0. 019) and DBil( r =-0. 643,P = 0. 011). Conclusion There are reductions in the positive expression of BSEP,MDR3,and MRP2 in each subtype of bile duct injury type of DILI,which is one of the important mechanisms of cholestasis in DILI.
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