高热量饲料结合慢性应激致大鼠非酒精性脂肪肝病变过程的研究

The aggravated process of nonalcoholic fatty liver disease induced by the combination of high-fat-sugar diet and chronic stress in rats

为观察不同作用时间下非酒精性脂肪肝(NAFLD)相关因子的改变,研究高热量饲料结合慢性应激促进NAFLD病变的过程,将64只雄性大鼠分为正常对照组、高热量饲料(HFSD)组、慢性应激(EFNS)组及高热量饲料结合慢性应激(HFSD+EFNS)组。8周后,每组随机取8只动物,作为第1批实验动物;14周后,余下每组8只动物作为第2批实验动物,检测胰岛素抵抗、血液及肝组织脂质、氧化应激状态、肿瘤坏死因子α(TNF-α)及基因表达,计算肝指数。另外,取肝脏做病理切片,比较各组肝组织病理改变程度。结果显示,8周后大鼠出现胰岛素抵抗、脂质紊乱、氧化应激、炎症状态及肝指数增加。2种刺激只对肝脂质代谢紊乱有交互作用。14周后,大鼠NAFLD进一步恶化,对脂质紊乱、肝脂质代谢、炎症、氧化应激状态均有协同作用,肝组织切片也显示出现脂肪性肝炎。高热量饲料结合慢性应激促进NAFLD有一个发展过程,14周后能够诱导大鼠非酒精性脂肪肝模型的形成。

To observe the aggravated process of nonalcoholic fatty liver disease （NAFLD） induced by the com- bination of high-fat-sugar diet with chronic stress in rats, 64 male rats were divided into four groups： control group, high fat-high-sucrose diet group （HFSD）, electric foot shock and noise stress group （EFNS）, and high fat-high-sucrose diet plus electric foot shock and noise stress group （HFSD ＋ EFNS）. After growing for 8 weeks, eight rats in each group wer6 randomly taken as the first experimental batch and after 14 weeks, the remaining eight rats in each group were taken as the second experimental batch. Blood samples and liver were collected. In addition, histology of the liver was blindly determined by a pathologist. As results, insulin resistance, lipid disorders, oxidative stress, inflammation and increased liver index were discovered in the HFSD ＋ EFNS group after 8 weeks. A signifi- cant interaction between high fat-high-sucrose diet and chronic tress was detected only on liver lipid metabolic dis- order. After 14 weeks, NAFLD in the rats was aggravated. Significant interactions between high fat-high-sucrose diet and chronic tress were observed on lipid metabolic disorder, inflammation, and oxidative stress. Steatohepatitis was observed in HFSD ＋ EFNS group. In conclusion, the pathological change of NAFLD induced by the combination of high-fat-sucrose diet and chronic stress was a developmental process. The model of NAFLD was successfully in- duced by high fat-high-sucrose diet plus electric foot shock and noise stress after 14 weeks.