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(glutamic-pyruvic 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。
Effect of Ursolic Acid in Hippophae rhamnoides L.on Mice with Alcoholic Liver Disease Based on Intestinal FXR-FGF15 Pathway
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(D-LA)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.
ursolic acid in Hippophae rhamnoides L.alcohol liver diseasesmall intestinefibroblast growth factor 15(FGF15)farnesoid X receptor(FXR)bile acid
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