Effect Of Dexamethazone On The Expression Of The Hepatocellular And Placental ER, The Erythrocyte COMT In Pregnant Rats With Ethinyl Estradiol Induced Intrahepatic Cholestasis

Objective:To investigate the mechanisms of dexamethasone(DXM) in the administration to ethinyl estradiol induced intrahepatic cholestasis of pregnancy.Method:Forty clean SD female rats were randomly assigned into four groups(A,B,C and D)after mating successfully,ten in every group. From day 13 to day 16 of gestation,the rats in Group A were injected with the 0.1%solution of ethinyl estradiol(EE)in propylene glycol(PG) subcutaneously once a day at a dose of 2.5 ml·(kg·d)^-1in order to modulate the ICP animal models.The animals' tails were cut to get blood for TBA value on the 16^thday of gestation,a value of(37.7±6.0)mol·L^-1 or more suggests a cuccessful model,From the 17^thto the 20^thday of gestation,the animals in group A were intramuscularly injected with physiological saline(NS)once a day at a dose of 0.2 ml·(kg·d)^-1(control group of ICP).Rats in Group B were intramuscularly injected with dexamethasone(DXM)at a dose of 1mg·(kg·d)^-1after constituted the ICP animal models as group A(intervented group of ICP).Rats in Group C were injected with propylene glycol(PG)subcutaneously once a day at a dose of 2.5 ml·(kg·d)^-1from day the 13^thto the 16^thday of gestation,and were intramuscularly injected with physiological saline(NS)once a day at a dose of 0.2 ml·(kg·d)^-1from the 17^thto the 20^thday of gestation(control group of non-ICP).Rats in Group D were intramuscularly injected with dexamethasone(DXM)at a dose of 1mg·(kg·d)^-1after constituted the non-ICP animal models as group C(intervented group of non-ICP).All rats were dealed with caesarean section at the time we observed blood in the vagina:The amour of all fetals and the dead fetals,the length and weight of all fetals were recorded,the maternal erythrocyte levels of COMT were analyzed,the maternal serum levels of uE₃ were measured, the average optical density(AOD)of the estrogen receptor(ER)in the placental and the liver was analyzed.Results:(1)The fetal death rate of group A,B,C,D were 16.67%, 2.50%,2.43%and 2.38%respectively.The control group of ICP was significantly higher than the control group of non-ICP,the intervented group of ICP was significantly lower than the control group of ICP, P＜0.01.(2)The fetal length of group A,B,C,D were(4.02±0.51)cm, (4.61±0.48)cm,(5.03±0.39)cm and(4.54±0.36)cm respectively,the fetal weight were(3.99±0.61)g,(5.01±0.59)g,(5.46±0.54)g and(5.07±0.64)g respectively.The control group of ICP was significantly lower than the control group of non-ICP,the intervented group of ICP was significantly higher than the control group of ICP,the intervented group of non-ICP was significantly lower than the control group of non-ICp,P＜0.01. (3)The integrate of liver necrosis area in group A,B,C,D were (2.07±0.52),(0.96±0.21),(0.29±0.12)and(0.27±0.09)respectively,of placenta they are(2.86±0.64),(1.19±0.26),(0.25±0.08)and(0.22±0.07) respectively.The control group of ICP was significantly higher than the control group of non-ICP,the intervented group of ICP was significantly lower than the control group of ICP,P＜0.01.(4)Most of the positive signals of ER in placenta were located in cytoplasm and a little in cell nuclear,in liver were located on the membrane.The average optical density(AOD)of the placental and hepatic ER of the four groups were (92.6±8.1,76.3±6.9),(37.9±6.5,34.2±5.8),(40.7±7.3,36.3±6.1)and (20.4±5.6,19.8±5.2)respectively.The control group of ICP was significantly higher than the control group of non-ICP,the intervented group of ICP was significantly lower than the control group of ICP,the intervented group of non-ICP was significantly lower than the control group of non-ICP,P＜0.01.(5)The value of maternal erythrocyte COMT of the four groups were(7.2±1.6)nmol·(mlRBC·hr)^-1,(12.9±1.2)nmol·(ml RBC·hr)^-1,(11.6±1.9)nmol·(mlRBC·hr)^-1and(15.1±2.1)mol·(mlRBC·hr)^-1 respectively.The control group of ICP was significantly lower than the control group of non-ICP,the intervented group of ICP was significantly higher than the control group of ICP,the intervented group of non-ICP was significantly higher than the control group of non-ICP,P＜0.01.The value of the maternal serum uE₃ concentration of the four groups were (28.43±5.49)μg/L,(20.19±4.36)μg/L,(18.92±3.98)μg/L and(13.56±3.62)μg/L respectively.The control group of ICP was significantly higher than the control group of non-ICP,the intervented group of ICP was significantly lower than the control group of ICP,the intervented group of non-ICP was significantly lower than the control group of non-ICP, P＜0.01.(6)There were negative correlation between uE₃ and COMT (r₃=-0.381,P＜0.05).Conclusion:After dexamethasone administration,the ICP fetal death rate significantly decreased,the fetal length and fetal weight significantly increased.It may work through mechanisms as follows: 1.When the dexamethasone is used to treat ICP,it can significantly debase the expression of the estrogen receptor(ER)in the placenta and the liver,in order to decrease the sensitivity to the estrogen;2.it can significantly increase the value of the maternal erythrocyte catechol-O-methyl transferase(COMT),in order to increase the liver's ability to metabolize the estrogen.