麦角甾酮对小鼠急性酒精性肝损伤及肠道菌群群落组成的影响

Effects of Ergosterone on Acute Alcoholic Liver Injury and Gut Microbiota Community Composition in Mice

目的研究麦角甾酮对酒精引起的小鼠急性肝损伤的作用及其对肠道菌群群落组成的影响。方法将C57BL/6小鼠随机分成空白组、模型组、甘草酸二铵组(60 mg×kg^-1)、麦角甾酮低剂量组(30 mg·kg^-1)、麦角甾酮高剂量组(60 mg·kg^-1),每组10只。除空白组、模型组外,其余组按相应剂量灌胃10 d。第9~10天,除空白组外,其余各组均以每剂量12 h的间隔灌胃2剂50%酒精(10 mL·kg^-1)诱导造模。ELISA检测血清中天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(γ-GT)和肝脏中的谷丙转氨酶(ALT)、前白蛋白(PA)、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平,苏木精-伊红染色法观察肝组织病理变化,并使用16SrRNA基因测序分析技术分析麦角甾酮对小鼠肠道菌群的影响。结果麦角甾酮可显著降低小鼠血清中AST、γ-GT和肝组织中ALT、MDA的水平,显著升高肝组织中PA和SOD的水平,并可调节酒精引起的肠道菌群中门水平和属水平菌群丰富度的变化。结论麦角甾酮对小鼠酒精诱导的急性肝损伤具有保护作用,并且可通过调节肠道菌群来改善肝损伤。

OBJECTIVE To study the effect of ergosterone on acute liver injury in mice induced by alcohol and its effect on the composition of gut microbiota. METHODS C57 BL/6 mice were randomly divided into blank group, model group, diammonium glycyrrhizinate group(60 mg·kg^-1), low dose of ergosterone group(30 mg·kg^-1) and high dose of ergosterone group(60 mg·kg^-1), 10 in each group. Except for the blank group and the model group, the other groups were administrated with the corresponding dose for 10 d. On day 9–10, the other groups except the blank group were administered with two doses of 50% alcohol(10 mL·kg^-1) at 12 h intervals to induce a model. Levels of aspartate aminotransferase(AST), γ-glutamyl transpeptidase(γ-GT) in serum and alanine aminotransferase(ALT), prealbumin(PA), malondialdehyde(MDA), superoxide dismutase(SOD) in liver were detected by ELISA. Hematoxylin-eosin staining was used to observe liver tissue pathological changes, and the effect of ergosterone on mice intestinal flora was analyzed by 16 S rRNA gene sequencing analysis technology. RESULTS Ergosterone could significantly reduce the levels of AST, γ-GT in serum and ALT, MDA in liver tissue, and significantly increase the levels of PA and SOD in liver tissue. Ergosterone also could regulate the alcohol-induced changes gut microbiota in phylum and genus levels. CONCLUSION Ergosterone has a protective effect on alcohol-induced acute liver injury in mice, and can improve liver injury by regulating the gut microbiota.