维生素C通过调节PPAR-α靶基因抑制高脂饮食诱导非酒精性脂肪肝小鼠  

Vitamin C Inhibits the Nonalcoholic Fatty Liver Induced by High Fat Diet in Mice Regulating PPAR-α Target Gene

作　　者：那日苏[1] 张海峰[2] NA Risu;ZHANG Haifeng(Inner Mongolia Medical University,Department of Pathophysiology,Hohhot 010110,China;Inner Mongolia Medical University,Department of Physiology,Hohhot 010110,China)

机构地区：[1]内蒙古医科大学病理学教研室,呼和浩特010110 [2]内蒙古医科大学生理教研室,呼和浩特010110

出　　处：《中国现代应用药学》2021年第22期2791-2795,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：内蒙古自治区自然科学基金项目(2020MS08108);内蒙古自治区卫生计生科研计划项目(201701046);内蒙古医科大学科技百万工程项目(YKD2016KJBW018)。

摘　　要：目的探讨维生素C是否通过调节PPAR-α靶基因抑制高脂饮食诱导非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)小鼠模型。方法C57BL/6小鼠随机分为对照组、NAFLD组和维生素C组。每组均为10只小鼠。对照组采用普通饲料连续喂养15周;NAFLD组采用高脂饲料连续喂养15周;维生素C组采用高脂饲料及维生素C连续喂养15周。喂养15周后,利用代谢测量、组织学和基因表达检查NAFLD相关因素。结果与NAFLD组小鼠相比,补充维生素C可抑制NAFLD小鼠体质量增加(P<0.05)。同时,维生素C组小鼠循环维生素C浓度显著高于NAFLD组(P<0.05)。维生素C可抑制肝脏脂肪变性(P<0.05)。同样,维生素C也可使NAFLD小鼠肝脏炎症、纤维化和凋亡相关基因mRNA水平降低(均P<0.05)。此外,维生素C小鼠血清丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇和低密度脂蛋白胆固醇水平低于NAFLD小鼠(均P<0.05)。最后,维生素C还能提高肝脏PPAR-α介导脂肪酸β氧化基因mRNA水平(均P<0.05)。结论维生素C对NAFLD小鼠体质量增加、肝脏甘油三酯积累,以及肝脏炎症、纤维化和凋亡有抑制作用,这一过程可能部分是通过上调PPAR-α靶基因表达介导的。OBJECTIVE To explore whether vitamin C could inhibit high-fat diet induced nonalcoholic fatty liver disease(NAFLD)mouse model by regulating PPAR-αtarget gene.METHODS C57BL/6 mice were divided into control group,NAFLD group and vitamin C group.Each group consisted of 10 mice.The control group was fed with normal diet for 15 weeks;the NAFLD group was fed with high-fat diet for 15 weeks;vitamin C group were fed with high-fat diet and vitamin C for 15 weeks.After 15 weeks of feeding,variables and determinants of NAFLD were examined using metabolic measurements,histology,and gene expression.RESULTS Compared to NAFLD group mice,administration of vitamin C to obese mice reduced body weight gain(P<0.05).Concomitantly,circulating vitamin C concentrations were significantly higher in vitamin C mice than in NAFLD mice(P<0.05).Vitamin C could inhibit hepatic steatosis(P<0.05).Similarly,vitamin C also reduced the mRNA levels of liver inflammation,fibrosis and apoptosis related genes in NAFLD mice(all P<0.05).In addition,serum alanine aminotransferase,aspartate aminotransferase,total cholesterol and low density lipoproteincholesterol levels in vitamin C mice were lower than those in NAFLD mice(all P<0.05).Vitamin C could also increase the mRNA level of PPAR-α-mediated fatty acidβoxidation gene in liver(all P<0.05).CONCLUSION Vitamin C can inhibit weight gain,liver triglyceride accumulation,liver inflammation,fibrosis and apoptosis in NAFLD mice,which may be partly mediated by up regulating PPAR-αtarget gene expression.

关 键 词：维生素C 非酒精性脂肪肝 小鼠 

分 类 号：R965.1[医药卫生—药理学]