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基于肠FXR-FGF15通路探讨沙棘熊果酸对酒精性肝损伤小鼠的影响

Effect of Ursolic Acid in Hippophae rhamnoides L. on Mice with Alcoholic Liver Disease Based on Intestinal FXR-FGF15 Pathway

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【作者】 李楠赵雪郭少龙张文龙戈娜李智林琰

【Author】 LI Nan;ZHAO Xue;GUO Shaolong;ZHANG Wenlong;GE Na;LI Zhi;LIN Yan;School of Public Health,Baotou Medical College;Institute of Nutrition and Food Health,Baotou Medical College;The First Affiliated Hospital of Baotou Medical College;

【通讯作者】 张文龙;戈娜;

【机构】 包头医学院公共卫生学院包头医学院营养与食品健康研究所包头医学院第一附属医院

【摘要】 该研究借助小鼠酒精性肝损伤模型,观察沙棘熊果酸补充对酒精性肝损伤(alcoholic liver disease,ALD)小鼠的改善效果,通过分析沙棘熊果酸对ALD小鼠肠法尼醇X受体(farnesoid X receptor,FXR)-成纤维细胞生长因子15(fibroblast growth factor 15,FGF15)通路的影响,探讨其可能的保护作用机制。结果表明,沙棘熊果酸能够改善ALD小鼠的肝脏、小肠组织炎症反应,降低ALD小鼠血清谷草转氨酶(aspartate transaminase,AST)、谷丙转氨酶(glutamicpyruvic transaminase,ALT)活性、总胆汁酸(total bile acids,TBA)、脂多糖(lipopolysaccharide,LPS)、D-乳酸(D-lactic acid,D-LA)含量,提高ALD小鼠胆盐水解酶(bile salt hydrolase,BSH)浓度。同时,沙棘熊果酸可提高ALD小鼠肠道FXR、FGF15、肝脏中成纤维细胞生长因子受体第4号(fibroblast growth factor receptor 4,FGFR4)蛋白表达量,降低肝脏中胆固醇7α-羟化酶(cholesterol 7α-hydroxylase,CYP7A1)蛋白表达。综上,沙棘熊果酸对酒精性肝损伤小鼠具有保护作用,其机制可能与调节肠FXR-FGF15通路有关。

【Abstract】 This study employed a mouse model of alcoholic liver disease(ALD)to observe the improvement effect of ursolic acid in Hippophae rhamnoides L. supplementation on mice with ALD. By analyzing the effect of ursolic acid in Hippophae rhamnoides L. on the farnesoid X receptor-fibroblast growth factor 15(FXR-FGF15)pathway in the intestine of ALD mice,the possible protective mechanism was explored. The results showed that ursolic acid in Hippophae rhamnoides L. could improve the inflammatory response of liver and small intestine tissue in ALD mice,reduce the activity of aspartate transaminase(AST)and glutamic-pyruvic transaminase(ALT),and decrease the content of total bile acids(TBA),lipopolysaccharide(LPS),and D-lactic acid(DLA)in the serum of ALD mice,with the increase in bile salt hydrolase(BSH)concentration in ALD mice.Meanwhile,ursolic acid in Hippophae rhamnoides L. could increase the expression levels of intestinal FXR,FGF15,and fibroblast growth factor receptor 4(FGFR4)proteins in ALD mice,and reduce protein expression levels of cholesterol 7α-hydroxylase(CYP7A1)in the liver. In summary,ursolic acid in Hippophae rhamnoides L. had a protective effect on ALD mice,and its mechanism might be related to the regulation of the intestinal FXR-FGF15 pathway.

【基金】 国家自然科学基金项目(82160618);内蒙古自治区卫生健康科技计划项目(202201373);内蒙古自治区自然科学基金项目(2023MS08041);包头医学院创新团队发展计划项目(bycxtd-11);包头医学院2023年研究生科研创新项目(bycx2023004、bycx2023007)
  • 【文献出处】 食品研究与开发 ,Food Research and Development , 编辑部邮箱 ,2025年02期
  • 【分类号】R285.5
  • 【下载频次】117
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