| Objective:This case-control study aims to detect and analyze the expression of bile acid transporters BSEP,MRP2,MDR3 in liver tissues of patients with intrahepatic cholestasis after liver transplantation,and to investigate the role of bile acid metabolism in its generation and development.Methods:By the case-control study,23 cases with hepatic dysfunction accompanied by severe jaundice after liver transplantation(case group)and 18 cases with hepatic hemangioma(control group)were selected.According to clinical manifestation,liver function and histological examination,patients in the case group were divided into two groups:cholestasis group(13 cases)and non-cholestasis group(10 cases).Clinic data and paraffin block of liver biopsy tissue were collected on all patients.It should be noted that liver tissue samples were obtained from the normal tissue beside hepatic hemangioma in control group.The liverspecimens were performed for histopathological and immunohistochemical examinations.Immunohistochemistry was performed to detect the expression of BSEP,MRP2 and MDR3 in the liver tissues of two groups.Semi-quantitative analysis was used to compare the difference expression of the above bile acid transporter in the case group and the control group,the cholestasis group and the non-cholestasis group.To explore the correlation between the bile acid transporters and liver function biochemical index after liver transplantation.Results:1.General data:there was no statistical difference in sex and age among cholestasis group,non-cholestasis group and control group(χ2=5.546,P=0.062,t=0.172,P=0.842).There was no difference in the time of liver dysfunction between cholestasis group and non-cholestasis group(Z=-0.558,p=0.577).2.Compared and analyzed the liver function indexes of cholestasis group,non-cholestasis group and control group:the liver function indexes ALT(107.8(61.5,174.0)vs 142.0(32.0,616.8),χ~2=23.248,P<0.001),AST(116.0(55.5,164.0)vs 126.0(61.5,249.8),χ~2=27.186,P<0.001),TBIL(192.1(163.6,300.15)vs294.2(223.7,522.7),χ~2=30.997,P<0.001),DBIL(135.4(92.1,234.3)vs159.9(119.9,258.2),χ~2=29.912,P<0.001),ALP(291.0(138.5,457.0)vs126.0(99.3,194.5),χ~2=26.783,P<0.001),GGT(351.0(202.5,446.5)vs 149.0(69.8,297.3),χ~2=29.434,P<0.001)of cholestasis group and non-cholestasis group were not statistically significant,but the two groups were statistically significant compared with normal control group(P<0.05).3.In the control group,the structure of hepatic lobule was clearly visible,the cytoplasm was abundant,the arrangement of hepatocytes was regular and the nucleus was centered,but in cholestasis group and non-cholestasis group,the structure of hepatic lobular was disorder,hepatocytes were significant edema degeneration,and small vesicular fatty degeneration were observed,Nuclear deflection,scattered in point necrosis.4.The expression of BSEP,MRP2,MDR3 in liver tissue.⑴BSEP:BSEP was highly expressed in the control group,the expression rate was 100%,but the expression rate and intensity of the case group were reduced, compared with control group,both of the differences were statistically significant(P<0.001,P=0.011).⑵MRP2:MRP2 was highly expressed in the control group,the expression rate was 100%,but the intensity of MRP2 was reduced in the case group,the difference between them have no statistical difference(χ~2=4.065,P=0.131).⑶MDR3:The positive expression rate of MDR3 in the control group was 100%,significantly higher than that in the case group,compared with control group,both of the differences were statistically significant(P<0.001,P=0.021),but the score difference between two groups was statistically significant(P=0.504).5.The correlation between the expression of BSEP,MRP2,MDR3 and liver function index:No significant correlation was observed between expressions of BSEP,MRP2,MDR3 and ALT,AST,AKP,GGT,TBIL,DBIL.We only found certain positive correlation between MDR3 and GGT(r=0.585,R~2=0.340,P=0.036),and a negative correlation between BSEP and AST in cholestasis group(r=-0.559,R~2=0.312,P=0.047).Conclusion:1.Accompanied by severe jaundice after liver transplantation,the patients who with abnormal liver function bile acid transporters BSEP,MDR3 protein expression have been downgraded,but the expression of MRP2 has no significant downgraded.2.No significant correlation was seen between intrahepatic cholestasis after liver transplantation and the abnormal expression of BSEP,MRP2 and MDR3.The molecular mechanism of those patients with intrahepatic cholestasis after liver transplantation still needs more investigations.3.BSEP(bile acid transporters)is negatively related to the AST which mainly exists in the mitochondria.It prompts that the lower expression of BSEP probably associated with liver cell necrosis.Moreover,there is a positive relation between MDR3expression and GGT.It prompts that the up-regulated of MDR3 expression is associated with bile duct cell hyperplasia and increased freed of GGT. |
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