仙灵骨葆单独及与奥美拉唑联合应用的肝毒性研究

The hepatotoxicity of Xian-Ling-Gu-Bao and its combination with Omeprazole in mice

目的考察仙灵骨葆及其与奥美拉唑联用对小鼠的肝毒性。方法雄性C57小鼠随机分为空白对照组、仙灵骨葆低和高剂量组(308、 2 464 mg/kg)、奥美拉唑组(8.22 mg/kg)及仙灵骨葆低、高剂量联用奥美拉唑组。各组连续给药27周,其中联用组先灌胃给予仙灵骨葆13周,再同时腹腔注射给予奥美拉唑14周。每周测定小鼠体重,末次给药后12 h处死小鼠,测定肝脏重量、肝系数及血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶活性,观察肝组织形态学变化,RT-PCR法检测肝脏Cyp1a2、Cyp3a11、Cyp2c37等主要药物代谢P450酶基因表达水平。结果各给药组小鼠体重增长率、肝脏重量均低于空白对照组。仙灵骨葆及其联用奥美拉唑对谷丙转氨酶、谷草转氨酶、碱性磷酸酶活性影响较小,但可造成肝组织炎细胞浸润并且能显著增加小鼠肝脏Cyp1a2、Cyp2c37 mRNA的表达。结论连续给予小鼠27周仙灵骨葆引起以肝组织炎细胞浸润为特征的肝损伤,仙灵骨葆联合奥美拉唑小鼠肝损伤程度与单用仙灵骨葆相当。

Objective To investigate the hepatotoxicity of Xian-Ling-Gu-Bao (XLGB) and its combination with Omeprazole (OME) in mice. Methods Male C57 mice were randomly divided into six groups:control group,XLGB low or high dose group (L-XLGB,308 mg/kg,H-XLGB,2 464 mg/kg),OME group (8.22 mg/kg) and L-XLGB or H-XLGB combined OME group.Except the control group,all the mice were orally treated with XLGB for 27 weeks.OME was injected intraperitoneally to the mice at the 13 th week during the treatment.The body weight of mice was determined every week.Mice were sacrificed 12 hours after the last administration.The hepatotoxicity was evaluated by examination of liver weight,liver coefficient,serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase activities and the liver histopathology changes.The hepatic P450 mRNA expression was measured by RT-PCR. Results The body growth rate and liver weight of mice in each administration group was lower than that in the control group.The serum transaminases were not significantly changed in XLGB or in combination with OME treated groups,however,inflammatory cell infiltration was observed and expressions of Cyp1a2 and Cyp2c37 mRNA were significantly increased in the liver of these groups. Conclusion Administration of XLGB for 27 weeks caused chronic inflammations in the liver of mice.The combination of XLGB and OME does not increase the hepatotoxicity when compared with the XLGB alone.