Iwaki Tomomichi, Ishizaki Kaoru, Kinoshita Shuji, Tanaka Hideki, Fukunari Atsushi, Tsurufuji Makoto, Imada Teruaki
Research Laboratory III (Immunology), Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
World J Gastroenterol. 2007 Oct 7;13(37):5003-8. doi: 10.3748/wjg.v13.i37.5003.
To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.
Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d. UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment.
At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 +/- 77.5 U/L vs 333.6 +/- 50.4 U/L and 254.3 +/- 35.5 U/L, respectively, P < 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.
The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.
研究熊去氧胆酸（UDCA）对仓鼠鹅去氧胆酸（CDCA）诱导的肝损伤的影响，并阐明肝损伤与肝脏胆汁酸谱之间的相关性。
通过在仓鼠饲料中给予0.5%（w/w）CDCA 7天来诱导肝损伤。在实验的最后3天给予UDCA（50mg/kg和150mg/kg）。
实验结束时，血清丙氨酸氨基转移酶（ALT）升高超过10倍，并且通过组织学证实存在肝损伤。肝脏中观察到胆汁酸明显增加。总胆汁酸量增加约三倍，并伴有疏水性胆汁酸、CDCA和石胆酸（LCA）的增加。UDCA（50mg/kg和150mg/kg）改善了肝脏组织学，血清ALT水平显著降低（分别为679.3±77.5U/L对333.6±50.4U/L和254.3±35.5U/L，P<0.01）。UDCA降低了疏水性胆汁酸的浓度，结果肝脏中总胆汁酸水平降低。
结果表明UDCA改善了仓鼠口服CDCA诱导的肝损伤。UDCA的保护作用似乎源于疏水性胆汁酸CDCA和LCA浓度的降低，这些胆汁酸在肝脏中积累并表现出细胞毒性。
