复方甘草酸单铵和异甘草酸镁对化学损伤人肝细胞的保护作用

Comparison of protective effects of compound ammonium glycyrrhetate and magnesium isoglycyrrhizinate on D-galactosamine-and carbon tetrachloride-injured human hepatocytes

目的:研究2类甘草甜素药物对半乳糖胺(D-GalN)和四氯化碳(CCl4)损伤培养人肝细胞(L-02)的保护作用及差异.方法:培养L-02,用复方甘草酸单铵(compound ammonium glycyrrhizin,CAG)和异甘草酸镁(magnesium isoglycyrrhizinate,MI)分别进行保护后,再经D-GalN或CCl4处理.观察肝细胞生长状态、测定AST、LDH酶活力、及细胞内谷胱甘肽(GSH)含量.从而评价CAG和MI对D-GalN和CCl4损伤L-02的保护作用差异.结果:浓度为1g/L的CAG和MI均能提高细胞的存活率,显著抑制D-GalN和CCl4所致的AST及LDH释放.CAG抑制D-GalN和CCl4所致的AST与LDH效果显著好于MI(均P<0.05);浓度为1g/L的CAG和MI均能显著抑制2种化学损伤细胞内的GSH降低(CCl4损伤:7.59±1.27,5.23±0.70vs3.33±0.40;D-GalN损伤:7.93±0.36,5.40±0.52vs3.77±0.45,P<0.01或0.05),CAG效果明显好于MI.结论:1g/L的CAG和MI2种药物对D-GalN和CCl4致人肝细胞损伤均有保护作用,其机制与抑制GSH降低相关.2种甘草甜素药物相比较,CAG保护肝细胞效果好于MI.

AIM： To compare the protective effects of compound ammonium glycyrrhetate （CAG） and magnesium isoglycyrrhizinate （MI） on D-galactosamine （D-GalN）and carbon tetrachloride （CCl4）-injured human hepatocytes （L-02）. METHODS： After L-02 cells were treated withCAG and MI, respectively, they were incubated with CCl4 or D-GalN to induce cell injury. Cell growth was observed under an inverted microscope. The activity of aspartate aminotransferase （AST） and lactate dehydrogenase （LDH） and the content of glutathione （GSH） in culture supematants were determined. RESULTS： At a concentration of 1g/L, both CAG and MI could improve the survival rate of cells, significantly inhibit D-GalN- and CCl4- induced release of AST and LDH and intracellular GSH depletion, and increase D-GaIN- and CCl4-induced decrease in mitochondrial membrane potential. Both of the CAG and MI can inhibit D-GalN and CCl4-induced release of AST End LDH and intracellular GSH depletion （CCl4：7.59 ± 1.27, 5.23 ± 0.70 vs 3.33 ± 0.40; D-GalN： 7.93 ± 0.36, 5.40 ± 0.52 vs 3.77 ± 0.45, P 〈 0.01 or 0.05）. CONCLUSION： At a concentration of 1g/L, both CAG and MI can exert protective effects on D-GalN and CC14-injured human hepatocytes perhaps via a mechanism that is associated with improving intracellular GSH depletion. CAG is superior to MI in protecting injured L-02 hepatocytes.