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目的:对比研究18α-甘草酸,18β-甘草酸及二者联合用药对小鼠急性肝损伤的保护作用,并筛选二者联合用药的最佳配伍比例。方法:小鼠随机被分为正常组,模型组,18α-甘草酸,18β-甘草酸低、中、高剂量组(15,30,60 mg·kg~(-1)),联合用药给药剂量均为60 mg·kg~(-1),联合用药1(18α-甘草酸-18β-甘草酸1∶3)组、联合用药2(18α-甘草酸-18β-甘草酸2∶3)组、联合用药3(18α-甘草酸∶18β-甘草酸1∶1)组。在造模前各治疗组ip给药7 d,1次/d,其他各组ip生理盐水;末次给药1 h后,除正常组ip生理盐水外,其他各组均ip 0.1%四氯化碳(CCl_4)花生油(20 m L·kg~(-1))建立CCl_4诱导小鼠急性肝损伤模型,观察18α-,18β-甘草酸高、中、低剂量(15,30,60 mg·kg~(-1))组,联合用药3个不同配伍比例组对急性肝损伤小鼠血清中和肝组织中丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST)水平的影响,并检测肝组织匀浆中超氧化物歧化酶(SOD)活力及丙二醛(MDA)含量,同时筛选二者联合用药的最佳配伍比例。结果:与正常组比较,模型组血清AST,肝组织AST,ALT,MDA水平明显升高,SOD活力显著降低(P<0.01),提示造模成功。与模型组比较,18α-甘草酸组,18β-甘草酸组均可降低小鼠血清中AST,肝组织AST,ALT活力,MDA含量,升高肝组织中SOD活力;比较二者对急性肝损伤小鼠的保护作用,结果 18β-甘草酸组对肝组织中AST,ALT水平影响优于18α-甘草酸组,其他指标无显著性差异;二者联合用药的最佳配伍比例为2∶3,其对肝组织中AST活力及MDA含量的影响均优于单用18α-或18β-甘草酸治疗组。结论:18α-与18β-甘草酸可保护急性肝损伤小鼠,后者保护作用比前者强,二者配伍的最佳比例是2∶3,其对AST,MDA水平影响优于单用18α-或18β-甘草酸。
OBJECTIVE: To compare the protective effects of 18α-glycyrrhizin, 18β-glycyrrhizinate and their combination on the acute liver injury in mice and to screen the best combination ratio of the two drugs. Methods: The mice were randomly divided into normal group, model group, 18α-glycyrrhizinic acid, 18β-glycyrrhizic acid low, medium and high dose groups (15, 30 and 60 mg · kg -1) Dose of 60 mg · kg ~ (-1), combination therapy 1 (18α-glycyrrhizinate-18β-glycyrrhizic acid 1: 3) group and combination therapy 2 (18α-glycyrrhizinic acid-18β- , Combination therapy 3 (18α-glycyrrhizic acid: 18β-glycyrrhizic acid 1: 1) group. Before treatment, the rats in each treatment group were administrated with ip for 7 d, once / d, and the other groups were treated with ip saline. After 1 h of the last administration, except for normal saline, the other groups were ip 0.1% Acute liver injury induced by CCl_4 in mice was induced by carbon tetrachloride (CCl_4) and peanut oil (20 m L · kg -1). The high, middle and low doses of 18α- and 18β- ~ (-1)) group and the combination of three different compatibility groups on serum levels of ALT and AST in mice with acute liver injury Liver homogenate superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, while screening the combination of the two best compatibility ratio. Results: Compared with the normal group, the levels of serum AST, AST, ALT and MDA in the model group were significantly increased and the SOD activity was significantly decreased (P <0.01), suggesting that the model was successful. Compared with the model group, 18α-glycyrrhizin group and 18β-glycyrrhizinate group could reduce AST, AST, ALT activity and MDA content in liver tissue and increase SOD activity in liver tissue, The protective effect of the mice, the results 18β-glycyrrhizinate group of liver AST, ALT levels better than 18α-glycyrrhizin group, other indicators no significant difference; the best combination of the two drugs ratio of 2: 3, Its effect on AST activity and MDA content in liver tissue were better than that of 18α- or 18β-glycyrrhizinate alone group. CONCLUSION: 18α- and 18β-glycyrrhizinate can protect mice with acute hepatic injury, the latter is more protective than the former. The best ratio of compatibility between them is 2: 3, which has a better effect on AST and MDA than the 18α- Or 18β-glycyrrhizinic acid.