蛋氨酸-胆碱缺乏饮食诱导的非酒精性脂肪性肝炎小鼠模型的建立及动态监测

A mouse model of non-alcoholic steatohepatitis induced by feeding a methionine-choline-deficient diet:establishment and dynamic monitoring

目的:研究蛋氨酸-胆碱缺乏(MCD)饮食诱导的非酒精性脂肪性肝炎(NASH)小鼠肝脏脂肪变性及炎症发生、发展的病理特点.方法:将40只C57/BL6小鼠随机分成2组,分别喂养MCD饮食(模型组)和对照蛋氨酸-胆碱充足(MCS)饮食(空白组),于造模的第1-5周动态连续取材,小鼠血清ALT、AST、TG及肝TG等生化指标通过全自动生化分析仪进行测定,肝脏标本通过油红O、HE染色对脂肪变性及炎症进行评分.结果:MCD饮食喂养2-3wk后,肝脏病理切片可见脂肪变及炎症,小鼠血清ALT(U/L)、AST(U/L)明显升高,与空白组相比有统计学差异(133.9±6.3vs47.3±1.3;154.3±24.6vs109.2±50.4,均P<0.05).在第3周时,模型组血清TG(mmol/L)含量较空白组明显降低(0.97±0.14vs1.45±0.32,P<0.01),而在第5周时,模型组肝TG(mmol/L)含量较空白组明显升高(1.50±0.22vs0.98±0.16,P<0.01).肝脏炎症坏死以腺泡1区为主为重,5wk时肝内纤维化表现开始出现.结论:MCD饮食诱导的NASH小鼠模型重复率高,造模2-3wk时模型稳定性最好.

AIM：To establish a mouse model of non-alcoholic steatohepatitis（NASH）by feeding a methionine-choline-deficient（MCD）diet and to dynamically monitor the pathological features of hepatic steatosis and inflammation in these mice.METHODS：Forty mice were randomly divided into two groups and fed an MCD diet or a me-thionine-choline-sufficient（MCS）diet.At weeks 1 to 5,these mice were sacrificed to take serum samples for biochemical measurements and liver samples for HE staining and oil red O staining to grade the degree of fatty change and inflam-mation.RESULTS：Steatosis and inflammation could be seen in mice fed an MCD diet for 2-3 wk.Serum ALT（U/L）,AST（U/L）levels increased signifi-cantly（133.9±6.3 vs 47.3±1.3;154.3±24.6 vs 109.2±50.4,both P0.05）,whereas TG（mmol/L） levels decreased（0.97±0.14 vs 1.45±0.32,P0.01）at week 3 in rats fed an MCD diet than in those fed an MCS diet.At wk 5,TG（mmol/L） levels in the liver increased significantly in rats fed an MCD diet than in controls（1.50±0.22 vs 0.98±0.16,P0.01）.Fibrosis could be seen at week 5 in mice fed an MCD diet.CONCLUSION：A mouse model of NASH has been created successfully by feeding an MCD diet.