中文摘要：

目的 探讨自噬在高脂饮食诱导的大鼠非酒精性脂肪性肝病（NAFLD）发生发展过程中的可能作用.方法 高脂喂养SD大鼠24只作为模型组,普通饮食18只作为对照组,于4、8、12周末分批处死.检测体重、肝湿重、肝功能、脂代谢等指标,肝组织HE、油红O染色评价病理学改变.透射电镜观察大鼠肝细胞的自噬现象.实时荧光定量PCR （qRT-PCR）检测自噬基因ATG7、Beclin1、微管相关蛋白1轻链3（microtubule-associated protein 1 lightchain3,LC3）mRNA水平表达变化.结果 与同时点对照组比较,模型组小鼠体重、肝湿重增加,油红O染色面积、密度增加.HE染色显示随造模时间延长出现不同程度脂肪变伴炎症灶,12周末80％达到NASH诊断标准（NAS≥5）,伴明显气球样变和轻度窦周纤维化.电镜图片显示自高脂饮食4周开始均有自噬泡出现.自噬基因ATG7、Beclin1、LC3-Ⅰ、LC3-Ⅱ自高脂饮食开始均有不同程度的上调,8周升至最高,较正常饮食组差异有统计学意义,（P＜0.05）.12周开始下降,与正常饮食组比,无明显差异.结论 高脂喂养SD大鼠可建立非酒精性脂肪肝病大鼠模型.自噬相关基因伴随NAFLD的发生发展呈动态变化表达,自噬参与了非酒精性脂肪肝的发生发展过程.

英文摘要：

Objective To investigate the expression and significance of autophagy related gene in rats with non-alcoholic fatty liver disease （NAFLD）.Methods In vivo model of NAFLD was established in SD rats by high fat diet （model group,n =24）,while the rats with normal food were set as control group （n =18）.The rats of each group were sacrificed at the end of 4,8,12 weeks respectively.Body weight,liver wet weight,liver function,liver lipid metabolism and other indicators were measured.Hepatic histology was evaluated by hematoxylin-eosin （HE） staining and oil red O staining.The identification of autophagy were morphologically visualized by transmission electron microscopy （TEM）.The expression of autophagy related gene ATG7,beclin1,microtubule-associated protein 1 lightchain3 （LC3） were detected by real-time quantitative RT-PCR （qRT-PCR） for mRNA levels.Result ① Compared with the control group at the corresponding time point,the weights of the mice and their livers.②Hepatic oil red O staining areas and density in high fat diet group all increased.HE staining revealed different degrees of macrosteatosis accompanied with intralobular inflammatary foci.With a remarkable histological change of NASH （typical hepatocellular ballooning and perisinusoidal fibrosis） about 80% of mice from high fat diet group had NASH [NAFLD activity score （NAS） ≥5] at the end of 12 weeks.③ TEM pictures showed that autophagy bubble appeared since high fat diet feeding for 4 weeks.④ The relative expression of ATG7,Beclin1,LC3-Ⅰ,LC3-Ⅱ at mRNA level were up-regulated after high fat diet,and reached their peak at the end of 8 weeks when compared with the control group.The differences can be applied to statistical significance （P 〈 0.05）.The expression of these autophagy related genes in rats of high fat diet group were down-regulated at the end of 12 weeks,which had no difference the control group.Conclusion ①High fat diet feeding is able to induce a rat model of NAFLD.②The expression level of au