Department Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, Korea.
Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea.
J Korean Med Sci. 2019 Jan 3;34(2):e14. doi: 10.3346/jkms.2019.34.e14. eCollection 2019 Jan 14.
The heterogeneity of histological findings in preclinical diet-induced nonalcoholic fatty liver disease (NAFLD) animal models is highly challenging. Here, we aimed to evaluate the feasibility and stability of repeated liver biopsy in NAFLD animal models.
Heterogeneity of diet-induced NAFLD was evaluated at different time points in 52 high-fat diet (HFD), 35 methionine choline-deficiency diet (MCD), and 166 western diet (WD) induced NAFLD mice. Serial liver biopsies (left lateral, right medial, and left medial lobes) were performed monthly for up to 3 months. Mortality rates and changes in food intake, body weight, and liver enzymes were assessed.
At 12 weeks, of the HFD animals, 14% and 30% did not develop steatosis and lobular inflammation, respectively; of the MCD animals, 7% did not develop lobular inflammation; and of the WD animals, 14% and 51% did not develop steatosis and lobular inflammation, respectively. The mortality rate of repeated liver biopsy was 1.62% (2/123 mice died). Repeated liver biopsy can be used to trace disease progression. Although body weight, food intake, and liver enzymes slightly changed after biopsy, all recovered within a week. Repeated liver biopsy did not affect the degrees of inflammation and steatosis of the other liver lobes.
The diet-induced NAFLD models were quite heterogeneous. Our results suggest that the repeated liver biopsy before treatment was applicable and stable in this NAFLD animal study.
临床前饮食诱导非酒精性脂肪性肝病（NAFLD）动物模型的组织学表现存在很大的异质性。本研究旨在评估 NAFLD 动物模型中重复肝活检的可行性和稳定性。
在 52 只高脂肪饮食（HFD）、35 只蛋氨酸胆碱缺乏饮食（MCD）和 166 只西方饮食（WD）诱导的 NAFLD 小鼠中，不同时间点评估饮食诱导的 NAFLD 的异质性。每月进行 3 次重复肝活检（左外侧、右内侧和左内侧叶），持续 3 个月。评估死亡率以及食物摄入量、体重和肝酶的变化。
在 12 周时，HFD 动物中分别有 14%和 30%的动物未发生脂肪变性和肝小叶炎症；MCD 动物中分别有 7%和 93%的动物未发生肝小叶炎症；WD 动物中分别有 14%和 51%的动物未发生脂肪变性和肝小叶炎症。重复肝活检的死亡率为 1.62%（123 只小鼠中有 2 只死亡）。重复肝活检可用于追踪疾病进展。尽管活检后体重、食物摄入量和肝酶略有变化，但均在一周内恢复。重复肝活检不会影响其他肝叶的炎症和脂肪变性程度。
饮食诱导的 NAFLD 模型存在较大异质性。本研究结果表明，在该 NAFLD 动物研究中，治疗前重复肝活检是可行且稳定的。
