| Objective: To study the expression level of FXR and BSEP in hepatocellular/placental tissue in late pregnancy rats with progesterone and or estradiol benzoate (EB) induced.Methods:60 SD rats pregnant for 15 days were randomly divided Into four group: control group, group A,,group B and group C.and given the subcutaneously injection of estradiol benzoate(EB),progesterone or appropriate volume of NS for 5 days.In control group, the rats were given NS,In group A ,the rats were given EB;.In group B,the rats were given progesterone; In group C,the rats were given progesterone and (EB).venous blood was sampled for the measurement of serum ALT,AST,ALP,TBA,TBIL,DBIL,IBIL level for twice(before given medication,before delivery). Liver and placenta were taken for histological analysis with light microscope by H&E staining after delivery and the physiological index of the fetal rats has entering into statistic.The expression of FXR/BSEP in liver and placenta was analyzed by immunohistochemical method (SP).Results: The serum levels of ALT,AST,ALP,TBA,TBIL,DBIL,IBIL in the experiment group rats increased significantly (p<0.05) and control group had no changes (p>0.05).The physical indexs of fetal rats were analyzed,and results indicated that control group was better than experiment group(p<0.05). In group A,B,C,there are obvious histopathological changes in liver indicated that intrahepatic cholestasis was induced by EB in pregnant rats.In experiment group,the degrees of FXR in the liver were significantly higher (p<0.05);but the BSEP were lower (p<0.05) contrast with control group. In placenta,existed the expression of FXR /BSEP too.Conclusion: Estradiol benzoate is the best candidate for inducing animal model of ICP,progesterone too.the severity of intrahepatic cholestasis and liver hispathology changes is obvious corralation with given estradiol benzoate and progesterone. The incidence of abortion, fetal death and stillbirth also increase.The augment of FXR expression in liver and down-regulating of BSEP by estrogen or progesterone may be the pathogenesis of intrahepatic cholestasis for pregnancy rats. Several progesterone metabolites are able to induce trans-inhibition of BSEP and the subsequent trans-inhibition of BSEP and thesubsequent toxicity induced by the accumulation of BAs,which may play a role in the etiopathogenesis of ICP. Progesterone metabolism disorder may cause concentration of UCB raised,may be involved in the aetiology of ICP,Progesterone can reinforcement action of estradiol benzoate. |
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