槲皮素对MRCD60纯化饲料诱导的非酒精性脂肪肝病的干预效果

Effects of quercetin on non-alcoholic fatty liver induced by MRCD60 purified feed

旨在探讨槲皮素(quercetin,QCT)对MRCD60纯化饲料诱导的小鼠非酒精性脂肪肝病(non-alcoholic fatty liver,NAFLD)的干预效果。将24只SPF级健康雄性C57小鼠随机分为4组,每组6只,正常饮食小鼠作为空白对照组(Con),MRCD60纯化饲料喂养作为模型组(MRCD60),MRCD60纯化饲料和25 mg/kg QCT喂养作为QCT低剂量组(QCT1),MRCD60纯化饲料和50 mg/kg QCT喂养作为QCT高剂量组(QCT2),QCT1组和QCT2组在MRCD60喂养3周后再加入QCT继续喂养3周;饲养6周后,检测各组小鼠血清中丙氨酸氨基转氨酶(ALT)、天门冬氨酸氨基转氨酶(AST)以及肝脏组织中总胆固醇(TC)、甘油三酯(TG)的含量;苏木素-伊红染色和油红O染色观察大鼠肝脏组织的病理学变化;实时荧光定量PCR法检测各组小鼠肝脏组织炎症相关基因肿瘤坏死因子(TNF-α),白介素6(IL-6)和白介素1β(IL-1β)mRNA水平的变化;免疫荧光检测各组肝脏中F4/80蛋白表达的变化;免疫组化检测各组小鼠肝脏中4-羟基壬烯醛(4-HNE)含量的变化。结果:与Con组相比,MRCD60组小鼠肝脏体积增大,颜色由红润变为深棕色,肝脏重量和肝脏指数增加,TG和TC含量增加,ALT和AST活性增加,大量脂质堆积,肝脏TNF-α、IL-6和IL-1βmRNA水平和F4/80蛋白含量升高,还原型谷胱甘肽(GSH)含量下降,丙二醛(MDA)和4-HNE含量升高;与MRCD60组相比,QCT1、QCT2组均显著减少肝脏脂质堆积,抑制肝脏炎症,降低肝脏氧化应激。综上,QCT可以改善MRCD60纯化饲料诱导的NAFLD小鼠肝脏脂质沉积、病理损伤、肝脏炎症和氧化应激。

To investigate the effect of quercetin(QCT)on non-alcoholic fatty liver disease(NAFLD)induced by MRCD60 purified feed,a total of 24 healthy male C57 mice with SPF grade were obtained and randomly divided into 4 groups with 6 mice in each group.The mice of the control group(Con)were fed with normal diet,and those of the model group(MRCD60)were fed with MRCD60 purified feed.Those of the QCT1 group were fed with MRCD60 purified feed and 25 mg/kg QCT.Those of the QCT2 group were fed with MRCD60 purified feed and 50 mg/kg.MRCD60 feeding for the QCT1 and QCT2 groups continued for 3 weeks and then QCT was added to the feed for another 3 weeks.After 6 weeks of experiment,the contents of ALT and AST in the serum and TC and TG in liver tissue samples collected from the mice were detected.Pathological changes in liver were observed by hematoxylin-eosin and oil red O staining.Real-time PCR was used to detect the mRNA levels of TNF-α,IL-6 and IL-1βin liver.The expression of F4/80 protein in liver was detected by immunofluorescence.The con⁃tent of 4-HNE in liver was detected by immunohistochemistry.The results were as follows:compared with the control group,the color changed from red to dark brown,and the liver volume,liver weight and liver index were increased in the MRCD60 group.MRCD60 feeding increased TG and TC contents in liver,serum ALT and AST activities of the organ,increased a large amount of lipid accumulation in the or⁃gan,increased its TNF-α,IL-6 and IL-1βmRNA levels and F4/80 protein contents.Also,MRCD60 feeding decreased GSH content in liver,but increased its MDA and 4-HNE contents.QCT supplementation at doses of 25 and 50 mg/kg significantly reduced lipid accumula⁃tion in liver,inhibited liver inflammation and reduced liver oxidative stress.In conclusion,QCT improved NAFLD induced by MRCD60 puri⁃fied feed.