[Effects of ursodeoxycholic acid on the liver plasma membrane fluidity, hepatic glutathione concentration, hepatic estrogen receptors and progesterone receptors in pregnant rats with ethinylestradiol and progesterone induced intrahepatic cholestasis].
OBJECTIVE
To explore the effects of ursodeoxycholic acid (UDCA) on the fluidity of hepatic plasma membrane, glutathione concentration in liver, hepatic estrogen receptors and progesterone receptors in pregnant rats with ethinylestradiol and progesterone induced intrahepatic cholestasis.


METHODS
sixty clean SD pregnant rats were selected and divided into three groups at random. Since the 13th day of pregnancy after taking blood, normal group was injected subcutaneously with refined vegetable oil 2.5 ml x kg(-1) x d(-1). Control group and treatment group were injected subcutaneously with the solution of progesterone 75 mg x kg(-1) x d(-1) and 17-alpha-ethynylestradio 1.25 mg x kg(-1) x d(-1) till the 17th day. Since the 17th day control group, normal group were fedwish 0.9% natriichloridi solution 5 ml x kg(-1) x d(-1); Treatment group was fedwish UDCA 50 mg x kg(-1) x d(-1) every day. On the 21th day, all rats were killed. Then the livers were collected for study. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe. Glutathione concentration was measured by 5,5'-dithionbis (2-nitrobenzoic acid) (DTNB). Estrogen receptors and progesterone receptors were measured by flow cytometry.


RESULTS
(1) Hepatic plasma membrane fluidity and glutathione (GSH) concentration: significantly lower level of GSH concentration and higher fluorescence polarization (P) were detected in control group (GSH: 1.13 +/- 0.03, P: 0.149 +/- 0.008) in comparison with normal group (GSH: 2.11 +/- 0.07, P: 0.132 +/- 0.004, P < 0.05). However, Significantly higher level of GSH concentration and lower fluorescence polarization were detected in treatment group (GSH: 1.82 +/- 0.04, P: 0.141 +/- 0.006) in comparison with control group (P < 0.05). The level of GSH concentration and fluorescence polarization were no difference between treatment group and normal group. Hepatic estrogen receptors (ER) and progesterone receptors (PR): The expression of ER and PR in control group (ER: 89.4 +/- 8.4, PR: 112.3 +/- 11.6) were higher than that of other two groups (P < 0.05). The expression of ER and PR in treatment group (ER: 56.4 +/- 7.5, PR: 70.1 +/- 9.3) were lower than that of control group (P < 0.05). But there was no difference between treatment group and normal group (ER: 39.5 +/- 7.3, PR: 59.6 +/- 7.4; P > 0.05).


CONCLUSIONS
Ursodeoxycholic acid may be effective drug in treatment intrahepatic cholestasis of pregnancy.
Shi
Qing-yun
QY
Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliate of Capital University of Medical Sciences, Beijing 100050, China.
Kong
Bei-hua
BH
Ma
Kai-dong
KD
Zhang
Xiang-li
XL
Jiang
Sen
S
D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy* / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000633:toxicity; D005260:Female; D005978:Glutathione / Q000032:analysis*; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008560:Membrane Fluidity / Q000187:drug effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000378:metabolism; D011374:Progesterone / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004997:Ethinyl Estradiol; D011374:Progesterone; D014580:Ursodeoxycholic Acid; D005978:Glutathione