Abstract:

Abstract:Objective To establish intrahepatic cholestasis of pregnancy (ICP) models of rats and detect the expression of heme oxygenase-1(HO-1) in liver tissue of pregnant rats with ICP and   brain tissue of  fetal rats,and to explore the  pathogenesis of  ICP.Methods 40 pregnant  rats were randomly divide into experiment group and control group,20 rats in each group. From the 15th day after pregnancy,the  pregnant rats in experiment group were administered with estrogen and progestrone to induce ICP，while  the rats in control group were administered with vegetable oil.At the 21st day after pregnancy the rats were executed and the blood  samples were obtained to detect the biochemical indicators,and the pathologic changes in liver tissue of pregnant rats and brain tissue of  fetal rats were observed by  HE staining; the HO-1 expression in hippocampal CA1 section of  brain tissue of fetal rats was detected by immunohistochemistry  staining and image analysis. Results Compared with control group,the levels of serum alanine aminotransferas
es (ALT), total bile salt (TBA),aspartate amino transaminase(AST) of the pregnant rats in experiment group were significantly increased (P<0.01). The pregnant rats in experiment group showed  granule and vacuolization,natural hepatic foliole structure in liver;and the structural changes such as swelling,vacuolar degeneration,partial cells dissolution,and  disappearance in brain tissue of fetal rats were found;but there was no pathologic changes in control group. The immunohistochemistry staining and image analysis results showed that compared with control group,the number of  HO-1 immunoreaction positive cells in  brain tissue of fetal rats was significantly increased in experiment group,and  the HO-1 expression level in  experiment group was significantly decreased(P<0.05). Conclusion The expression of HO-1 in brain tissue of fetal rats with ICP is decreased,which suggests that HO-1 might be  important to cause fetal anoxia and death.

Key words: cholestasis,intrahepatic, heme oxygenase-1; , estrogen, progesterone; , fetal brain, rats,SD