T0901317对apoE基因敲除小鼠肝脂质蓄积及肝固醇调节元件结合蛋白-1c表达的影响

目的本文研究肝X受体(LXR)激动剂T0901317对apoE基因敲除小鼠肝脏脂质蓄积及肝脏固醇调节元件结合蛋白1-c(SREBP-1c)表达的影响。方法52只雄性apoE基因敲除小鼠被随机分成4组:基础组(n=10)对照组(n=14)、LXR激动剂治疗组(n=14)、d.LXR激动剂预防组(n=14)。各组小鼠均被给予高脂/高胆固醇饲料喂养;基础组小鼠被赋形剂灌胃处理8周;对照组小鼠被赋形剂灌胃处理14周;LXR激动剂治疗组小鼠在前8周被赋形剂灌胃处理,后6周被T0901317灌胃处理;LXR激动剂预防组小鼠被T0901317灌胃处理14周。使用HE和油红O染色方法观察小鼠肝脏脂质蓄积情况;采用实时定量PCR和蛋白质印迹方法分别检测肝脏SREBP-1cmRNA和蛋白质的表达。结果实验结果显示LXR激动剂治疗组和预防组小鼠肝脏脂质滴较对照组明显增多,组织结构排列逐渐紊乱(P<0.05);LXR激动剂治疗组和预防组小鼠肝脏SREBP-1cmRNA和蛋白质表达上调(P<0.05)。结论LXR激动剂T0901317能增加高脂高胆固醇饲料喂养的apoE基因敲除小鼠肝脏脂质蓄积并上调SREBP-1c表达。

Effects of T0901317 on lipid accumulation and the expression of sterol regulatory element binding protein-1c in the liver of apoE-/-mice

Objective To investigate the effect of T0901317 on lipid accumulation and the expression of sterol regulatory element binding protein-1c (SREBP-1c) in the liver of apoE-/- mice. Methods Male 8-week-old apoE-/- mice were randomly divided into four groups: baseline group (n = 10), vehicle group (n = 14), treatment group (n = 14) and prevention group (n = 14). All of the mice were fed a high-fat/high-cholesterol diet with or without LXR agonist T0901317 for 8 or 14 weeks. Lipid accumulation of the liver was observed by hematoxylin and eosin (HE) and oil red O staining. SREBP-1c mRNA and protein were determined by real-time quantitative PCR and western blot respectively. Results Lipid droplet of the liver in treatment and prevention group mice were markedly increased when compared with control group mice, liver structure became gradually inordinate (P < 0.05). SREBP-1c mRNA and protein expression in the liver of treatment and prevention group mice up-regulated when compared with control group mice (P < 0.05). Conclusion LXR agonist T0901317 can up-regulate the expression of SREBP-1c in apoE-/- mice fed with high- fat/high-cholesterol diet.