二氢杨梅素通过抑制脂质合成途径改善非酒精性脂肪性肝病

Dihydromyricin ameliorates non-alcoholic fatty liver disease by inhibiting lipid synthesis

目的探讨二氢杨梅素对非酒精性脂肪性肝病(NAFLD)的改善作用及其潜在作用机制。方法高脂饮食诱导的NAFLD模型建造成功后,使用随机数字表法将小鼠分为两组,一组通过灌胃的方法给予二氢杨梅素(100 mg·kg^-1·d^-1),另一组给予对应体积的生理盐水,持续给药4周。期间,每周测量体重、进食量。4周后,行葡萄糖耐量实验、胰岛素释放实验和胰岛素耐量实验。小鼠处死后,检测肝脏脂质沉积情况,并对血脂、肝功能及肝脏中脂代谢相关基因的表达情况进行分析。结果二氢杨梅素治疗后,高脂喂养小鼠体重明显降低,糖脂代谢、肝功能均有所改善,肝脏脂肪变性减轻、甘油三酯含量降低(t=2.161~7.315,P均<0.05)。此外,肝脏固醇调节元件结合蛋白-1c(SREBP-1c,t=3.2,P<0.05)和脂肪酸合酶(FASN,t=7.116,P<0.01)mRNA及蛋白表达水平均明显下调。结论二氢杨梅素通过降低SREBP-1c/FASN的表达进而抑制肝脏脂质从头合成途径而改善NAFLD。

Objective To explore the effect of dihydromyricin on the improvement of non-alcoholic fatty liver disease and its potential mechanism.Methods The mice of non-alcoholic fatty liver disease model induced by high fat diet were randomly divided into two groups using a random number table,one group was given dihydromyricin(100 mg·kg-1·d-1)by gavage,and the other group was given the corresponding volume of normal saline.During this period,body weight and food intake were measured weekly.After treatment for 4 weeks,the glucose tolerance,insulin release and insulin tolerance tests were measured.The lipid accumulation in the liver was detected and the level of serum lipid,the expression of lipid metabolism-related genes and liver functions were analyzed.Results After treatment with dihydromyricin,the mice had significantly lower body weight,better metabolic profiles and liver function.In addition,the mice treated by dihydromyricin had less steatosis and triglyceride content in liver(t=2.161-7.315,all P<0.05).The mRNA and protein expression levels of sterol regulatory element binding protein 1c(SREBP-1c,t=3.2,P<0.05)and fatty acid synthase(FASN,t=7.116,P<0.01)were significantly down-regulated.Conclusion Dihydromyricin can inhibit the de novo synthesis of liver lipids by reducing the expression of SREBP-1c/FASN and ameliorate non-alcoholic fatty liver disease.