鹅去氧胆酸对胆汁淤积孕鼠血生化指标、肝脏病理及胎鼠预后的影响

Effects of chenodeoxycholic acid on biochemical index,hepatic histology,and fetal prognosis in rats with intrahepatic cholestasis of pregnancy

目的以熊去氧胆酸(UDCA)为对比,研究法尼醇X受体(FXR)激动剂——鹅去氧胆酸(CDCA)对妊娠期肝内胆汁淤积(ICP)孕鼠血生化指标、肝脏病理及胎鼠预后的影响。方法建立ICP孕鼠模型,将孕17d的SD大鼠40只随机分成对照组、ICP组、UDCA组和CDCA组。比色法检测用药前后各组丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST),碱性磷酸酶(ALP)和总胆酸(TBA)水平,光镜下观察孕鼠肝脏病理学变化,记录胎鼠身长、尾长、体重及死胎数。结果ICP组ALT、AST、ALP、TBA明显高于对照组(P<0.008 3);与ICP组比较,UDCA组ALT、AST、ALP明显降低(P<0.008 3),但TBA无明显改善(P>0.008 3);CDCA组ALT、AST、ALP无明显改善(P>0.008 3),但TBA显著降低(P<0.008 3);2治疗组胎鼠的身长、尾长、体重及死亡率与ICP组比较均无统计学差异(P>0.008 3)。光镜下见ICP组肝细胞肿胀变性,肝血窦变窄,胆管扩张;UDCA组肝细胞脂肪变性明显,小叶结构正常;CDCA组小部分肝细胞脂肪变性,小叶结构正常。结论UDCA能改善ICP孕鼠肝功能指标,但不能有效降低血胆汁酸水平及胎鼠死亡率;CDCA能明显降低胆汁酸,促进胆汁酸代谢,但其安全性还有待确定。

AIM To compare the effects of the potent endogenous farnesoid X receptor （FXR） ligand- chenodeoxycholic acid （CDCA） with ursodeoxycholic acid （UDCA） on biochemical index, hepatic histology, and fatal prognosis in rats with intrahepatic cholestasis of pregnancy （ICP） . METHODS Forty pregnant Sprayne Dawley rats with 17-day gestation were randomized into four groups： control group （normal saline 2.5 mL· kg^-1 body weight daily）, ICP model group （estradiol benzoate （EB）, 2.5 mg·kg^-1 daily）, UDCA group （EB 2.5 mg·kg^-1 and UDCA 50 mg·kg^-1 daily）, CDCA group （EB 2.5 mg·kg^-1 and CDCA 100 mg·kg^-1 daily）,respectively for 5 d. Serum aminotransferase （ALT, AST, ALP） and total bile acid （TBA） levels were analyzed before and after the administration of the drug. The pathologic changes of the maternal liver, the length of the fetal body and tail, its bodyweight, and the fatality after administration were recorded. RESULTS Rats with estradiol benzoate （ICP model group） showed high level of ALT, AST, ALP, TBA, and fetal death as compared to controls. During the administration of UDCA, ALT, AST and ALP declined with no change in TBA and fetal fatality. With the administration of CDCA, TBA was reduced significantly, but there is no difference in fetal length of body and tail, weight, and fetal fatality as compared to the ICP model group. CONCLUSION UDCA can improve biochemical index with the exception of TBA and the fetal fatality; CDCA dramatically decrease TBA by improving the metabolism of bile acid but could not decrease the fatality, its clinical safety should be paid attention to.