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A rabbit model of pediatric nonalcoholic steatohepatitis:The role of adiponectin

摘要AIM: To create a rabbit model of pediatric nonalcoholic steatohepatitis (NASH) and to evaluate the role of adiponectin in the process. METHODS: Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups: (1) the normal control group ( n = 10) was fed with standard diet for 12 wk; (2) the model group A ( n = 11); and (3) model group B ( n = 11) were fed with a highfat diet (standard diet + 10% lard + 2% cholesterol) for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α were measured. RESULTS: Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis.Compared with the normal control group, there were significant increases in model groups A and B in weight gain (1097.2 ± 72.3, 1360.5 ± 107.6 vs 928.0 ± 58.1, P < 0.05, P < 0.01), liver weight (93.81 ± 6.64, 104.6 ± 4.42 vs 54.4 ± 1.71, P < 0.01), Lg (ALT) (1.9 ± 0.29, 1.84 ± 0.28 vs 1.60 ± 0.17, P < 0.01), and Lg (TG) (1.03 ± 0.24, 1.16 ± 0.33 vs 0.00 ± 0.16, P < 0.01). Weight gain was much more in model group B than in model group A (1360.5 ± 107.6 vs 1097.2 ± 72.3, P < 0.05). But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines (IL-6 and TNF-α) increased in model group B compared with that of control and model group A (IL-6: 1.86 ± 0.21 vs 1.41 ± 0.33, 1.38 ± 0.42, P < 0.01; TNF-α: 1.18 ± 0.07 vs 0.66 ± 0.08, 0.86 ± 0.43, P < 0.01, P < 0.05),whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control (adiponectin:A: 21.87 ± 4.84 and B: 21.48 ± 4.60 vs 27.36 ± 7.29,P < 0.05. IL-10: A: 1.72 ± 0.38 and B: 1.83 ± 0.39 vs 2.26 ± 0.24, P < 0.01). Lg (TC) and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. CONCLUSION: This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.

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作者单位 Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China [1]
分类号 R5
栏目名称 ORIGINAL ARTICLES
DOI 10.3748/wjg.15.912
发布时间 2009-04-17
基金项目
浙江省自然科学基金 Major Programs of Zhejiang Provincial Medical and Health Science and Technology & Chinese Ministry of Health Special Major Programs of Zhejiang Provincial Science and Technology
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