高脂饮食致大鼠非酒精性脂肪性肝炎肝纤维化模型

Rat model of nonalcoholic steatohepatitis with fibrosis by a fat-rich diet

目的:通过高脂饮食建立大鼠非酒精性脂肪性肝炎肝纤维化模型。 方法:以普通饲料+100g/kg猪油+20g/kg胆固醇组成的高脂饲料喂养SD大鼠,并设普通饲料喂养大鼠作为对照,在实验4,8,12,16,24wk分批处死。测定血脂和血清转氨酶,并通过HE染色和VG苦味酸染色观察肝脏肝细胞脂肪变性、炎症和纤维化程度。 结果:2组大鼠体重均呈进行性增长,模型组大鼠4wk起肝指数(肝脏湿质量/体质量)明显升高,血清TCh水平8wk起明显升高,12～24wk血清ALT明显升高。模型组4wk大鼠出现肝细胞脂肪变性,8wk表现为单纯性脂肪肝,12-24wk进展为脂肪性肝炎,且24wk所有造模大鼠均出现窦周纤维化,1例出现桥接纤维化。 结论:持续24wk的高脂饮食就可建立大鼠非酒精性脂肪性肝炎肝纤维化模型,该方法简便实用,成功率高。

AIM: To establish a rat model of nonalcoholic steatohepatitis (NASH)by feeding of a fat-rich diet.METHODS: SD rats were chronically fed a fat-rich diet that consisted of fat-rich diet, 100 g/kg lard oil and 20 g/kg cholesterol. The rats of normal control group were fed the normal diet. These rats sacrificed at the 4,8,12,16 and 24 wk of the experiment respectively. The serum levels of lipid and aminotransferase were measured. And the degrees of hepatic steatosis, inflammation, and fibrosis were observed with H-E and V-G stains.RESULTS:The body weights of rats gradually grew in both of two groups, and the liver index increased markedly from the 4 wk in model group. Moreover, the serum TCh levels inceased from 8 wk and the ALT levels increased at 12-24 wk significantly in model group. The livers presented the pathology of hepatocyte steatosis at the 4 wk and fatty degeneration at 8 wk in rats of model group. And from 12 to 24 wk of experiment, the livers developed steatohepatitis gradually. At 24 wk of fat-rich diet feeding, all model rats developed perisinosodial fibrosis, and bridge fibrosis presented in one rat.CONCLUSION: The rat model of nonalcoholic steatohepatitis with fibrosis can be established by feeding of fat-rich diet for 24 weeks. This method is simple, reliable and effective.