熊去氧胆酸对肝内胆汁淤积孕鼠卵黄囊细胞膜流动性及胎盘组织谷光甘肽含量的影响

Effect of ursodeoxycholic acid on visceral yolk sac cell membrane fluidity and placental glutathione concentration in pregnant rats with intrahepatic cholestasis

目的 探讨熊去氧胆酸 (ursodeoxycholicacid ,UDCA)的应用对胆汁淤积症 (ICP)孕鼠脏层卵黄囊细胞膜脂质流动性及胎盘组织谷光甘肽 (glutathione,GSH)含量的影响。 方法 选择妊娠SD大鼠 6 0只 ,随机分成三组 ,每组 2 0只 :(1)自妊娠第 13天起对照组孕鼠皮下注射精制植物油 2 .5ml/ (kg·d) ,ICP非治疗组和治疗组分别皮下注射孕酮 75mg/ (kg·d)和 17α 乙炔雌二醇1.2 5mg/ (kg·d) ,直至孕 17d。 (2 )自妊娠第 17天起 ,对照组、ICP非治疗组孕鼠行生理盐水 5ml/ (kg·d)灌胃 ,治疗组孕鼠UDCA 5 0mg/ (kg·d)灌胃。 (3)三组孕鼠均于妊娠第 2 1天处死 ,记录死胎数并计算死胎率 ,取出子宫 ,仔细分离胚胎脏层卵黄囊膜 ,制备脏层卵黄囊细胞悬液 ,应用 5 ,5’ 二硫代双(二硝基苯甲酸 )直接法测定GSH的含量 ;应用 1,6 二苯已三烯荧光标记法测定细胞膜脂质流动性。 结果 (1)孕鼠胚胎脏层卵黄囊细胞膜脂质流动性及胎盘组织GSH含量 :ICP非治疗组GSH含量、偏振度P值分别为 :(1.12± 0 .0 2 )mmol/gprot、0 .32 2± 0 .0 0 2 ;对照组分别为 :(1.5 6±0 .0 7)mmol/ gprot、0 .2 81± 0 .0 0 3;治疗组分别为 :(1.38± 0 .0 3)mmol/gprot,0 .171± 0 .0 0 3。ICP非治疗组与对照组相比 ,GSH含量明显下降 (P <0 .0

Objective To explore the effects of ursodeoxycholic acid (UDCA) on the fluidity of rat visceral sac and placental glutathione (GSH) concentration in rats with intrahepatic cholestasis. Methods Sixty rats were randomly divided into 3 groups (20 in each). Refined vegetable oil 2.5 ml/(kg·d) was given to the control group since the 13 days of pregnancy. The ICP treatment and non treatment group received either progesterone 75 mg/(kg·d) or 17α ethynylestradiol 1.25 mg/ (kg·d) from the 13th to 17th day, respectively. From the 17th day, the control and non treatment group were fed with 0.9% nitrachloride solution 5 mg/(kg·d) and the treatment group with UDCA 50 mg/(kg·d). All rats were sacrificed on the 21st day. The visceral yolk sac cell membrane and GSH concentration were measured Results The concentration of GSH in the ICP non treatment group (1.12±0.02 mmol/g protein) was significantly lower than that of the treatmentgroup (1.38±0.03 mmol/g protein) and the control group (1.56±0.07 mmol/g protein) ( P <0.05). The fluore scence polarization in the ICP non treatment group (0.322±0.002) was significantly higher than that of the treatment group (0.171±0.003 mmol/g protein) ( P <0.05)and no significant difference was found between the non treatment and control group (0.281±0.003) ( P >0.05). The fetal death rate in treatment group (9.55%) and control group (1.97%) was significantly lower than that of the non treatment group (20.47%) ( P <0.05), but the rate in the treatment group remained higher than the control group. Conclusions UDCA can reduce the fetal death rate in rat with ICP and UDCA may be an effective treatment for ICP.