摘要
目的观察高脂饮食诱导的大鼠非酒精性脂肪性肝病进展中肝脏脂代谢关键调控基因表达的变化。方法大鼠随机分为正常组10只和模型组30只,后者又分为4、8和12周3个时相点,正常组喂以普通饲料,模型组喂以高脂饲料;模型组分别在实验第4、8和第12周末随机处理10只,正常组大鼠在第12周末处理。采用荧光实时定量PCR检测各大鼠肝组织PPARα、PPARγ、SREBP、CPT-1、FAS、ACC mRNA表达。结果模型组大鼠在喂养高脂饲料4周后即出现血脂紊乱、肝细胞脂肪变;在连续喂养8～12周血脂异常持续存在,肝细胞脂肪变程度明显加重,且出现逐渐加重的肝组织炎细胞浸润和血清ALT、AST水平增高;从4～8周、12周模型组大鼠肝组织PPARα、PPARγ、CPT-1mRNA表达逐渐降低,且均较正常组明显降低(P<0.05,P<0.01);而SREBP、FAS、ACC mRNA表达水平则逐渐增加,且均较正常组明显增高(P<0.05,P<0.01)。结论高脂饮食诱导的NAFLD大鼠存在明显的脂质代谢紊乱,而调控脂代谢的SREBPs及PPARs信号通路可能在NAFLD的发生发展中起重要作用。
Objective To observe the expressions of key regulatory genes of the lipid metabolism in rat liver during the development of non - alcohol fatty liver disease （NAFLD） induced by fat - rich diet. Methods Forty SD rats were randomly divided into 2 groups. The ten rats in the normal group were fed with normal diet and painlessly killed at the end of the 12th week for following detections. The 30 rats in the disease group were fed with fat- rich diet and 10 were painlessly killed at the ends of the 4th, 8th and 12th week, respectively. The mRNA expressions of PPARα、PPARγ, SREBP, CPT -1, FAS and ACC genes in all the rats＇ livers were detected by realtime PCR. Results Dyslipidemia and hepatic steatosis occurred in the rats from the diseases group at the end of the 4th week after fat - rich diet. At the ends of the 8th and 12th weeks, dyslipidemia still existed and the hepatic steatosis aggravated accompanied with gradually infiltrating of inflammatory cells and increase of the serum levels of ALT and AST. Compared with those detected at the end of 4th week, the mRNA expressions of PPARα、PPARγand CPT - 1 in the liver significantly decreased at the both ends of the 8th and 12th weeks and were lower than those in rats with normal diet （ P 〈 0.05, P 〈 0. O1 ） , whereas the mRNA expressions of SREBP, FAS and ACC obviously increased at the latter two time points and were higher than those in rats with normal diet （P 〈 0.05, P 〈 0.01 ）. Conclusion Obvious lipid metabolism disorders occur in rat＇s NAFLD induced by fat - rich diet and the signaling pathways of SREBPs and PPARs which regu- late the lipid metabolism may play important roles in the development of NAFLD.
出处
《医学研究杂志》
2013年第5期157-160,共4页
Journal of Medical Research
