[熊去氧胆酸对乙炔雌二醇和孕酮诱导的妊娠大鼠肝内胆汁淤积症肝脏质膜流动性、肝谷胱甘肽浓度、肝雌激素受体和孕酮受体的影响]

[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].

作者信息

Shi Qing-yun, Kong Bei-hua, Ma Kai-dong, Zhang Xiang-li, Jiang Sen

机构信息

Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliate of Capital University of Medical Sciences, Beijing 100050, China.

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2003 Nov;38(11):680-2.

PMID:14728856

Abstract

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).

CONCLUSION

Ursodeoxycholic acid may be effective drug in treatment intrahepatic cholestasis of pregnancy.

摘要

目的

探讨熊去氧胆酸（UDCA）对炔雌醇和孕酮诱导的妊娠大鼠肝内胆汁淤积症肝细胞膜流动性、肝脏谷胱甘肽浓度、肝脏雌激素受体和孕激素受体的影响。

方法

选取60只清洁级SD孕鼠，随机分为3组。自妊娠第13天采血后，正常组皮下注射精制植物油2.5 ml·kg⁻¹·d⁻¹。对照组和治疗组皮下注射孕酮溶液75 mg·kg⁻¹·d⁻¹和17-α-炔雌醇1.25 mg·kg⁻¹·d⁻¹至第17天。自第17天起，对照组、正常组每日灌胃0.9%氯化钠溶液5 ml·kg⁻¹·d⁻¹；治疗组每日灌胃UDCA 50 mg·kg⁻¹·d⁻¹。第21天，处死所有大鼠，取肝脏进行研究。以1,6-二苯基-1,3,5-己三烯（DPH）为探针，采用荧光偏振法测定膜流动性。采用5,5'-二硫代双（2-硝基苯甲酸）（DTNB）法测定谷胱甘肽浓度。采用流式细胞术测定雌激素受体和孕激素受体。

结果

（1）肝细胞膜流动性和谷胱甘肽（GSH）浓度：与正常组（GSH：2.11±0.07，P：0.132±0.004）相比，对照组（GSH：1.13±0.03，P：0.149±0.008）GSH浓度显著降低，荧光偏振（P）值升高（P<0.05）。然而，与对照组相比，治疗组（GSH：1.82±0.04，P：0.141±0.006）GSH浓度显著升高，荧光偏振值降低（P<0.05）。治疗组与正常组GSH浓度和荧光偏振值无差异。肝脏雌激素受体（ER）和孕激素受体（PR）：对照组（ER：89.4±8.4，PR：112.3±11.6）ER和PR的表达高于其他两组（P<0.05）。治疗组（ER：56.4±7.5，PR：70.1±9.3）ER和PR的表达低于对照组（P<0.05）。但治疗组与正常组之间无差异（ER：39.5±7.3，PR：59.6±7.4；P>0.05）。