目的 探讨胆淤方对1，4-二氢-2，4，6-三甲基-3，5-吡啶二甲酸二乙酯（DDC）诱导胆汁淤积小鼠血清胆汁酸代谢的影响。方法 40只雄性C57BL/6J小鼠随机分为4组：对照（N）组、DDC模型（M）组、奥贝胆酸（O）组、胆淤方（D）组，每组10只。N组小鼠用普通饲料喂养，M、O和D组小鼠用DDC饲料喂养，连续6周。造模第3周开始药物干预，O组ig予奥贝胆酸溶液（0.03 g·kg^-1），D组ig予胆淤方药液（33 g·kg^-1），M组和N组予相同体积的双蒸水。干预4周，收集小鼠血清和肝组织，试剂盒检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、总胆红素（TBIL）和总胆汁酸（TBA）水平，HE染色观察肝组织炎症反应，CK19染色观察细胆管增生反应，天狼腥红染色观察纤维化，采用液质联用技术检测血清胆汁酸谱。结果 O组和D组ALT、AST、ALP、TBA、TBIL水平均较M组显著下降（P＜0.05）；D组ALT、AST水平较O组显著下降（P＜0.05）。D组小鼠肝组织炎症反应、纤维化及细胆管增生较M组减轻。D组血清初级胆汁酸胆酸（CA）和ω-鼠胆酸（ω-MCA）水平均较M组显著下降（P＜0.001）；D组血清次级胆汁酸甘氨胆酸（GCA）、牛磺胆酸（TCA）、牛磺熊去氧胆酸（TUDCA）、牛磺鹅去氧胆酸（TCDCA）、牛磺去氧胆酸（TDCA）、牛磺猪去氧胆酸（THDCA）较M组显著下降（P＜0.05、0.01、0.001），O组的CA、ω-MCA、TCDCA、GCA和TCA水平较M组显著下降（P＜0.001），D组血清TUDCA水平较O组下降更加显著（P＜0.05）。热图分析显示13种胆汁酸可将M与N组、O与M组、D与M组、D与O组血清胆汁酸谱两两区分。结论 胆淤方可改善肝内炎症反应，具有广泛的降胆汁酸作用。

Objective To investigate the effect of Danyu Recipe on the serum bile acid metabolism in mice with cholestasis induced by DDC. Methods 40 male C57BL/6J mice were randomly divided into four groups, 10 normal group (N), 10 model group (M), 10 obeticholic acid group (O), and 10 Danyu Recipe group (D). The mice in group N were fed with normal feed. Mice in the M, O and D groups were fed with DDC feed. Modeling was continued for six weeks. Drug intervention was started in the 3rd week of modeling. The O group was orally administered with Obeticholic acid 0.03 g·kg^-1, and the D group was orally administered with Danyu decoction 33 g·kg^-1. The mice in group M and group N were given the same volume of double distilled water by gavage. Mice were treated after four weeks of intervention, and mouse serum and liver tissue were collected. The serum bile acid profile of four groups was detected by liquid chromatography-mass spectrometry. Results The levels of ALT, AST, ALP, TBA and TBIL in O group and D group were significantly lower than those in M group (P < 0.05). The levels of ALT and AST in group D were significantly lower than those in group O (P < 0.05). There was no significant difference in the levels of ALP, TBA and TBIL in group D and group O. The intrahepatic inflammatory reaction, fibrosis and hyperplasia of small bile ducts in group D were less than those in group M. Serum primary bile acid CA and ω-MCA levels in group D were significantly lower than those in group M (P < 0.05). The levels of serum secondary bile acids GCA, TCA, TUDCA, TCDCA, TDCA, and THDCA in group D were significantly lower than those in group M (P < 0.05). The levels of GCA and TCA in group O were significantly lower than those in group M (P < 0.05). However, the level of serum TUDCA in group D was more significantly lower than that in group O (P < 0.05). Heat map analysis showed that 13 kinds of bile acids could distinguish the serum bile acid profiles of M and N groups, O and M groups, D and M groups, and D and O groups. Conclusion Danyu Recipe can improve the inflammatory response in the liver and has a more extensive effect on lowering serum bile acid.

R285.5

国家自然科学基金青年基金项目（81803874）