摘要
研究DHA单酰基甘油酯对小鼠急性酒精性肝损伤的保肝作用及机制.将雄性小鼠随机分为正常组、模型组、实验组(DHA单酰基甘油酯组)、阳性对照组(DHA三酰基甘油酯组和DHA乙酯组)5组.给药15 d后,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)含量,肝组织Toll样受体4(TLR4)、髓样分化因子(MyD88)、核转录因子κB(NF-κB)基因表达水平.观察肝组织病理性改变;分析小鼠粪便细菌多样性.DHA单酰基甘油酯能显著降低急性酒精肝损伤小鼠血清ALT、AST、ALP、TG、TC和LDL浓度,而显著增加HDL浓度,改善酒精引起的肝组织病理性改变,而且DHA单酰基甘油酯对小鼠肝损伤改善效果优于DHA三酰基甘油酯和DHA乙酯.此外,DHA单酰基甘油酯能显著抑制酒精肝损伤小鼠肝组织TLR4、MyD88、NF-κB基因表达,对酒精引起的肠道菌群紊乱具有一定恢复作用.DHA单酰基甘油酯对酒精诱导小鼠肝损伤具有一定保护作用,其机制可能与抑制TLR4/NF-κB通路和改善肠道菌群有关.
Abstract
In this paper,the protective effect and mechanism of DHA monoglyceride(DHA-MAG)on acute alcoholic liver injury in mice were studied.The male mice used in experiments were randomly divided into five groups of normal group,model group,experimental group(DHA-MAG)and two positive control groups(triacylglycerols group(DHA-TAG);ethyl esters group(DHA-EE).After drug administration for 15 days,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),triacylglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL)in mice serum were de-termined;meantime,the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor(MyD88),nuclear transcription factor-κB(NF-κB)of mice were examined.In addition,the histopathological changes of liv-er in mice were observed,and the intestinal bacteria diversities of feces were deeply analyzed.The obtained results indicated that the treatment by DHA-MAG significantly alleviated the acute alcohol-induced increases in serum ALT,AST,and ALP activities and reduced the levels of serum TG,TC and LDL in treated mice,while the level of serum HDL was increased.It was interesting to find that the trends of acute hepatic injury induced by alcohol were reduced after DHA-MAG treatment.Moreover,mice treated with DHA-MAG had a better protective effect on the liver injury induced by ethanol than those of treated with DHA-TAG and DHA-EE.Furthermore,DHA-MAG could significantly down-regulate the expression levels of TLR4,MyD88 and NF-Kb genes,and mitigate dysbiosis of intestinal flora induced by alcohol.Based on these results,it was concluded that DHA-MAG had protective effects on mice liver injury induced with alcohol by inhibiting TLR4/NF-κB pathway and maintaining the stability of intestinal flora.
基金项目
福建省科技厅引导性项目(2020N0008)
福建师范大学碳中和研究院开放基金项目(TZH-2022-03)
维普
万方数据