α-与β-甘草酸在小鼠体内分布的研究

Studies on distribution in mice tissues of α-Glycyrrhizic acid and β-Glycyrrhizic acid

目的 :探讨甘草酸 (glycyrrhizicacid ,GL)的两个差向异构体α GL和 β GL在小鼠体内的分布及其特征。方法 :运用HPLC UV法检测小鼠单次ivα GL或 β GL5 3mg·kg-1后 5、15、30、6 0和 180min时体内各组织脏器中的药物含量 ,比较、评价两者的分布差异及特征。结果 :α GL和 β GLiv后分布迅速 ,除血外 ,肝中含量最高 ,肺、肾、脂肪、心、卵巢、肠、脾、睾丸、肌肉中药物含量依次减小 ,脑中最低 ;肠肝循环的第二峰现象出现在 30min时 ;α GLiv后早期肝含量显著高于 β GL ,血及其余组织脏器药物含量明显低于 β GL或与其相近 ;随时间的延长药物含量迅速降低的同时肠浓度渐高 ,至 180min时α GL各组织脏器 (除肠外 )药物浓度接近或低于检测限 ,β GL则仍维持较高浓度 ,是峰值的 30 %～ 70 %。结论 :小鼠ivα GL后在体内呈肝分布特异性 ,转化成GA的速率高于 β GL ,无组织蓄积 ;而 β GL在体内分布广泛 ,代谢较慢 。

AIM: To examine the characters of distribution of two epimers of glycyrrhizic acid (GL) including α-GL and β-GL in mice. METHODS: After iv administration of a single 53.0 mg·kg -1 α-GL or β-GL in mice at 5, 15, 30, 60, and 180 min, the concentrations of α-GL or β-GL in some tissues were determined by HPLC-UV method, and the features of distribution of α-GL and β-GL were evaluated and compared. RESULTS: α-GL and β-GL were all quickly distributed. Except the plasma, the concentrations of α-GL and β-GL were higher in the liver than that in other tissues. The second peak of enterohepatic circulation could be observed at 30 min after iv administration. The concentration of α-GL in the liver was significantly higher than that of β-GL, but it was lower than or similar to that of β-GL in the plasma and other tissues after iv. Then the levels declined rapidly in all tissues but the intestine at 180 min after iv administration, meanwhile, β-GL maintained rather high concentrations in various tissues, which were all 30%-70% of the peaks. CONCLUSION: After iv administration, α-GL is target to the liver, and can be efficiently converted to more α-GA than β-GL, and it nearly has no accumulation in the tissues. The tissue distribution of β-GL in mice appears to be wild throughout the body, and the metabolism is slower than that of α-GL to accumulate in some tissues.