目的 考察甘草与昆布配伍对大鼠肝肾功能及血清指标的影响。方法 雄性SD大鼠随机分为4组，各组分别ig给予甘草提取物2.8 g/kg（相当于甘草生药材10.0 g/kg）、昆布提取物3.8 g/kg（相当于昆布生药材10.0 g/kg）、甘草-昆布合煎提取物6.8 g/kg（相当于甘草和昆布生药材各10.0 g/kg）和空白溶媒（对照）。连续ig给药17周后，检测各组大鼠体质量、脏器系数、血液生化指标、肝切片病理变化以及甘草次酸血药浓度。结果 甘草或昆布单用组较对照组大鼠丙氨酸转氨酶（AST）、天冬氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、胆碱酯酶（CHE）、总胆汁酸（TBA）和总胆红素（TBIL）水平显著降低（P<0.05），而甘草-昆布合用可逆转两药单用对AST、ALP、CHE、TBA、TBIL和直接胆红素（DBIL）的降低作用；甘草-昆布合用组大鼠体内甘草次酸血药浓度和暴露量显著高于甘草单用组。甘草、昆布单用或合用还导致大鼠体内电解质水平失衡，表现为血清中钠离子（Na⁺）、钾离子（K⁺）、氯离子（Cl^-）水平显著高于对照组。结论 甘草或昆布单用均具有保肝作用，甘草-昆布合用导致两药单用时的保肝作用减弱可能是其配伍"相反"原因之一，其机制可能与两药合用时甘草次酸血药浓度增加有关。

Objective To evaluate the effects of compatibility of Glycyrrhiza uralensis and Laminaria japonica on liver and kidney functions as well as serum indexes in rats. Methods A total of 24 male SD rats were randomly divided into four groups. Group 1 was served as control and only received vehicle. Group 2 and group 3 were orally dosed of G. uralensis extracts (2.8 g/kg) and L. japonica extracts (3.8 g/kg) once daily, respectively. Group 4 was orally dosed with 6.8 g/kg of G. uralensis-L. japonica extracts once daily. The experimental rats were treated corresponding extracts or vehicle for 17 weeks. During the experiment, the weight of rats, organ coefficient, biochemical indexes, and liver histopathological photograms in each group were measured. Meanwhile, plasma glycyrrhetinic acid concentration in G. uralensis extract group and G. uralensis-L. japonica extract group were observed. Results The water extraction components from G. uralensis and L. japonica groups could significantly reduce the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholinesterase (CHE), total bile acid (TBA), and total bilirubin (TBIL) comparing with control group (P < 0.05). While the G. uralensis-L. japonica extracts group could reverse these biochemistry indexes. G. uralensis-L. japonica extracts markedly increased the plasma concentration and exposure of glycyrrhetinic acid. Electrolyte metabolism balance was disordered after long-term treatment of G. uralensis, L. japonica and G. uralensis-L. japonica extracts, showing the level of sodium (Na⁺), potassium (K⁺), and chloride ion (Cl^-) in these three groups were significantly higher than that in control group. Conclusion These results indicated that G. uralensis or L. japonica extracts might has hepatoprotective effects. However, G. uralensis-L. japonica extracts attenuated the hepatoprotective effects, which might result from the increased plasma concentration of glycyrrhetinic acid.

江苏省方剂高技术研究重点实验室/江苏省中药资源产业化过程协同创新中心资助项目（FJGJS-2015-05）；"973"国家重点基础研究发展计划资助项目（基于十八反的中药配伍禁忌理论基础研究）子课题（藻戟遂芫具战草配伍关系与毒效表征的基础研究，2011CB505303）