白花丹素改善高脂饮食小鼠肝脏脂代谢并降低糖异生的研究

Study on Plumbagin Improves Liver Lipid Metabolism and Reduces Gluconeogenesis in Mice Fed with High Fat Diet

目的研究白花丹素(plumbagin,PLB)在非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)中的治疗效果。方法将成年C57BL/6J小鼠分为4组:对照组(标准饮食,15%脂肪),高脂肪饮食组(high fatty diet,HFD,58%脂肪),HFD+PLB(5 mg·kg−1·d−1)组,HFD+PLB(15 mg·kg−1·d−1)组。HFD造模6周,PLB共灌胃4周,随后处死小鼠。通过HE染色和油红染色研究小鼠肝脏脂肪堆积情况,通过qRT-PCR试验研究肝脏脂代谢和糖异生相关基因表达情况,最后通过Western blotting研究活化蛋白-1(activator protein,AP-1)相关亚基的表达情况。结果PLB可显著降低小鼠体质量和血液中葡萄糖水平,HE染色和油红染色结果显示PLB可显著降低小鼠肝脏脂质积累。PLB可显著降低脂肪代谢过程和糖异生相关基因表达,并可抑制AP-1亚基c-Jun,c-Fos和Fra1表达。结论PLB可显著抑制HFD小鼠肝脏细胞脂肪累积,维持脂肪代谢和葡萄糖稳态,并抑制AP-1炎症反应。

OBJECTIVE To investigate therapeutic effects of plumbagin(PLB)on nonalcoholic fatty liver disease(NAFLD).METHODS Adult C57BL/6J mice were divided into four groups:control group(standard diet,15%fat),high fat diet group(HFD,58%fat),HFD+PLB(5 mg·kg−1·d−1)group,HFD+PLB(15 mg·kg−1·d−1)group.The HFD model was established for six weeks,and PLB was administered four weeks.Then the mice were killed to study the lipid accumulation in the liver by HE staining and oil red staining.The effects of liver lipid metabolism and gluconeogenesis related gene expression were studied by qRT-PCR.Finally,the expression of activator protein(AP-1)related subunits were studied by Western blotting.RESULTS PLB could significantly reduce body weight and blood glucose level of mice.HE staining and oil red staining showed that PLB could significantly reduce the liver lipid accumulation of mice.PLB significantly reduced the expression of lipid metabolism and gluconeogenesis related genes,and inhibited the expression of AP-1 subunits c-Jun,c-Fos and Fra1.CONCLUSION PLB can significantly inhibit fat accumulation,maintain fat metabolism and glucose homeostasis,and inhibit the inflammatory response of AP-1 in liver cells of HFD mice.