A Study About The Regulatory Mechanism Of Dexamethasone In The Treatment Of Intrahepatic Cholestasis Of Pregnancy Rats

BackgroundIntrahepatic cholestasis of pregnancy(ICP)is a kind of clinical syndrome that occurs d uring pregnancy,such as : liver injury,elevated liver enzymes and total bile acid abnormali ties in pregnant women;fetal and neonatal hypoxia or death and so on.The previous resear ch indicates that the disease can induce bile acid complex gene regulatory networks abnor malities,which cause perinatal adverse prognostic outcomes,and it is difficult to determine in advance through the existing clinical techniques,how to use a good safe and effective tr eatment or prevention is a big problem to be solved.ObjectiveTo investigate the regulation of the farnesoid X receptor/ bile salt export pump in progesterone induced SD rats in pregnancy with intrahepatic cholestasis and intervention mechanism of dexamethasone.Methods45 clean level SD pregnant rats that have pregnant 10-14 days were randomly divided into 3 groups and each group of 15,(negative control group: control group,Positive control group: model group,treatment group),intraperitoneal injectio every day for one time: contr ol saline 2.5ml/kg/d,model group and treatment group were injected with Progesterone 225 mg / kg/d to establish animal model.Each group of pregnant rats were collected the heart blood 2ml in the 10 th and 15 th day in pregnancy to determination of blood biochemical par ameters.treatment group after successful modeling is intramuscular inject dexamethasone1 ml / kg/d in the 15-19 days of pregnancy,one time a day,and collect the heart blood 2mL in 20 th day of pregnancy to reserve.3 groups of pregnant rats immediately cesarean sectiontermination of pregnancy after near the time of labour,record the number of fetal rat and s tillbirth,measure fetal rats weight;and observe the pathological changes of pregnant rats li ver tissue,reversetranscriptase-olymerasechain reaction(RT-PCR)todetect the mRNA expression of FXR、BSEP and the proteinsexpression of the both by western blotting.Results(1)There was no significant difference in blood biochemical indexes before and after treatment in each group(P>0.05),Total bile acid(TBA)and Alanineaminotransferase(ALT)were significantly increased in the model group(P<0.05),the difference is statistically sig nificant before and after the intervention of dexamethasone(P<0.05).(2)HE staining: In the model group of pregnant rats the cells of portal area of liver edema,liver sinusoid narrow,a little liver cells fatty degeneration occurred;in the treatment group pregnant rat liver cells arranged in neat without edema,no steatosis,hepatic sinusoid gap is normal.(3)The stillbirth rate: model group is significantly higher than the control group,treatment group is significantly lower than the model group(P<0.05).(4)The weight of fetal rats in each group are compared:model group is significantly lower than the control group and treatment group,the difference is statistically significant(P<0.05).(5)The expression of FXR,FXR mRNA are up-regulated,BSEP and BSEP mRNA are down regulated in the model group of pregnant rats(P<0.05),While the expression of FXR,FXR mRNA is down regulated and BSEP,BSEP mRNA expression is up-regulated in the treatment group compared with model group(P<0.05).ConclusionThe regulation mechanism of dexamethasone intervention of ICP may be through reducing the expression of FXR in liver of pregnant rats and increase the expression of BSEP,r-educe the body’s sensitivity to progesterone and its metabolites,and plays a protective rolein cholestasis of pregnancy rat liver function,and effectively reduce the adverse prognosis of fetal rats.