目的 探索海藻-甘草反药配伍致大鼠肾毒性的内在机制。方法 大鼠随机分为对照组、海藻组、甘草组、海藻-甘草配伍组，经过连续ig给药4周的多次给药毒性实验，检测血清中尿素氮（BUN）、肌酐（Scr）、醛固酮、皮质醇及电解质水平，并进行肾脏组织病理学检查；用UPLC-TQ/MS法同时检测甘草中的6种主要成分在肾组织的分布情况；Western blotting法检测11β-类固醇脱氢酶（HSD11B2）在肾组织中的蛋白表达水平。结果 与对照组相比，海藻组大鼠的血清生化指标无明显变化，甘草组的血清中醛固酮水平显著降低（P<0.05），BUN、Scr显著升高（P<0.01）；海藻-甘草组的血清中醛固酮、K⁺、Cl^-水平显著降低（P<0.05、0.01），而BUN、Scr、皮质醇水平显著升高（P<0.05、0.01）。病理组织学检查表明，甘草组大鼠的肾脏组织有轻微的炎细胞浸润，海藻-甘草组有明显的炎细胞浸润并伴有蛋白管型。海藻-甘草组大鼠的肾脏组织中的甘草次酸分布明显高于甘草组（P<0.05）。与对照组相比，甘草组、海藻-甘草组大鼠的肾组织HSD11B2蛋白表达水平均显著降低（P<0.05、0.01），而海藻-甘草组更为显著。结论 通过增加甘草次酸在大鼠肾脏组织的积蓄，抑制肾脏组织中的HSD11B2的表达，造成醛固酮-皮质醇系统紊乱，可能是海藻-甘草反药组合产生肾毒性的主要机制。

Objective To study the toxicological mechanisms of the compatibility application of Sargassum pallidum and Glycyrrhiza uralensis on kidney in rats.Methods Rats were divided into control, Sargassum pallidum(S), Glycyrrhiza uralensis(G), and Sargassum pallidum-Glycyrrhiza uralensis extract (S-G) groups, which were respectively exposed (gavages) for 4 weeks.Then, the levels of blood urea nitrogen (BUN), serum creatinine (Scr), aldosterone, cortisol, and electrolytes in rat serum and pathological sections of kidney were detected.Six active contents of Glycyrrhiza uralensis in kidney of rats were detected by UPLC-TQ/MS method.The expression of HSD11B2 in kidney was detected by Western blotting.Results Compared with the control group, all biochemical indicators of S group had no obvious change.It was found that the level of aldosterone from G group and S-G group was significantly lower than that from control group (P<0.05, 0.01).In contrast to the control group, S. pallidum-G. uralensis extract led to significantly increased concentration of cortisol, BUN, and Scr in serum (P<0.05, 0.01).The level of K⁺ and Cl^- in S-G group was significantly lower than that in control group (P<0.05, 0.01).Pathological examination showed that the G group had mild inflammation infiltration, and a serious inflammatory response accompanied by protein tube was absolved in S-G group.Compared with the G. uralensis extract group, the combination of S. pallidum and G. uralensis significantly raised the concentration of glycyrrhetinic acid (GA) in kidney (P<0.05).When compared to that of control group, there was an inhibited expression of HSD11B2 in the kidney of L group and S-G group.Moreover, the expression of HSD11B2 in S-G group was markedly higher than that in G group (P<0.05).Conclusion The toxicity of S-G group was mainly result that increased accumulation of GA, and inhibited the expression of HSD11B2, which resulted the aldosterone-cortisol system disorders.