黄芪甲苷对实验性急性肝衰竭小鼠的保护作用

Protective effect of astragaloside IV against acute liver failure in experimental mice

目的研究黄芪甲苷对急性肝衰竭小鼠的早期治疗效果并探讨其可能机制。方法建立D-氨基半乳糖（D—GaIN）／脂多糖（LPS）诱导的小鼠急性肝衰竭模型，给予不同剂量黄芪甲苷预处理，观察各组小鼠存活率，以及对丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、肝组织病理变化、肝细胞凋亡的影响和对超氧化物歧化酶（SOD）、丙二醛的调节。满足方差齐性的采用LSD检验、方差不齐的采用Dunnett’s T3检验，生存分析采用Kaplan—Meier法进行统计学分析。结果与模型组比较，黄芪甲苷高剂量组小鼠48h存活率明显提高[2／15（13．3％）对比9／15（60％），P〈0．05]，血清ALT、AST水平均明显降低（P〈0．01），肝组织病理指数及肝细胞凋亡程度均减轻（P〈0．01），肝匀浆中丙二醛含量明显下降（P〈0．01），而SOD活力显著增强（P〈0．05）。结论高剂量黄芪甲苷对D—GalN／LPS致小鼠急性肝衰竭具有显著保护作用，其机制可能与抗细胞凋亡、抗氧化损伤有关。

Objective To investigate the clinical effect of astragaloside IV in the early treatment of mice with acute liver failure and possible mechanisms. Methods A mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide （D-Gal N/LPS） was established, and the mice were given astragaloside IV at different doses. The survival rate of mice, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels, liver histopathological changes, apoptosis of hepatocytes, and the expression of superoxide dismutase （SOD） and malondialdehyde （MDA） were measured in each group. The least significant difference test was used for data with homogeneity of variances, the Dunnett＇s T3 test was used for data with heterogeneity of variance, and the Kaplan-Meier method was used for survival analysis. Results Compared with the model group, the high- dose aslragaloside IV group had a significant increase in the 48-hour survival rate [60% （9/15） vs 13.3% （2/15）, P 〈 0.05], significant reductions in the serum ALT and AST levels （P 〈 0.01）, and significant reductions in liver histopathological indices and the degree of apoptosis of hepatocytes （P 〈 0.01）, as well as a significant reduction in the content of MDA in liver homogenate （P 〈 0.01） and a significant increase in the activity of SOD （P 〈 0.05）. Conclusion High-dose astragaloside IV has a significant protective effect against D-GalN/LPS-induced acute liver injury in mice, and its mechanisms may be associated with its effects against cell apoptosis and oxidative damage.