幼兔非酒精性脂肪肝炎模型的建立

目的：以高脂饲料喂养的幼兔模型模拟青春期前肥胖儿童非酒精性脂肪肝炎（nonalcoholic steatohepatitis，NASH）的形成，评价脂联素等炎症相关因子在NASH形成中的作用。方法：38只新西兰大耳兔根据饮食及喂养时间的不同分为：对照组、模型A组和模型B组。实验结束后，取肝脏进行HE染色、组织学诊断，取血清测血生化、脂联素、IL-6、IL-10、TNF-α浓度。结果：HE染色显示模型组大耳兔全部符合NASH病理特征。与对照组比较，模型组血清ALT、AST、TG、TC显著升高（P〈0．01），脂联素、IL-10下降（P〈0．05），两个模型组之间没有差异。前炎症因子IL-6、TNFα在模型B组明显高于模型A组和对照组，但是在模型A组与对照组之间没有差别。多元回归分析发现，肝细胞脂肪变性和TC是血清脂联素的两个独立决定因素，两者系数（8）分别为-0．97和-1．3，P值分别为0．038、0．006；常数项系数为27．89，P=0．000，决定系数（R^2）为0．294。结论：本实验所建立的幼兔NASH模型能较好地反映疾病形成的关键；血清脂联素能在一定程度上反映幼兔肝脏脂肪变性的严重度。

Establishment of rabbit model of juvenile nonalcoholic steatohepatitis

OBJECTIVE: To establish a rabbit model of juvenile nonalcoholic steatohepatitis (NASH) for further study. METHODS: Twenty-eight New Zealand rabbit pups were fed with a high-fat diet (standard diet+10 % lard+2 % cholesterol) for 8 or 12 weeks as the two model groups, and 10 rabbits were fed with standard diet as the controls. Liver tissue samples were collected for Heamatoxylin-Eosin staining and pathological examination. RESULT: Typical histological hepatic lesions of NASH were observed in both model groups. Compared with control group, model groups showed a significant increase in serum ALT, AST, TG, TC levels (P <0.01), and decrease in serum adiponectin, IL-10 levels (P <0.05), meanwhile there was no significant difference between two model groups. TC and the degree of liver fatty infiltration were independent determinants of serum adiponectin level by stepwise multiple regression, beta=-1.33, P=0.006 and beta=-0.97, P=0.038, respectively, R square equal to 0.294. CONCLUSION: The juvenile steatohepatitis rabbit model has been established and the level of adiponectin can partly reflect the severity of liver steatosis.