Zheng Wen, Liu Yuli, Shang Haibao, Zhang Yan, Ma Dongwei, Hou Ning, Wang Jue, Sun Xueting, Peng Ying, Pan Lin, Wang Zhilong, Tang Xinran, Xiao Rui-Ping, Zhang Xiuqin
1Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
2Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, 100871 China.
Diabetol Metab Syndr. 2018 Sep 10;10:68. doi: 10.1186/s13098-018-0370-1. eCollection 2018.
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic afflicting 20-30% in the general population. The animal model of NAFLD available at the present are less clinically relevant. In this study. We aimed to establish a NAFLD model of rhesus monkeys and develop an ultrasonographic steatosis score (USS) system to grade hepatic steatosis in this model.
We performed hepatic ultrasonography and blood biochemical tests on 86 rhesus monkeys with and without metabolic syndrome (MetS), among which 45 animals were further assessed by histopathological analysis.
The liver histological features of rhesus monkeys NAFLD were resemble to those of NAFLD patients. There was a close correlation between the histological steatosis grade and the USS (Spearman's coefficient, 0.705, p < 0.001). The USS sensitivity was 87.5% and the specificity was 94.6% when the cut-off was USS2. In addition, the prevalence of MetS was significantly higher in the USS2-3 group. Multiple risk factors of cardiometabolic disease, including obesity, insulin resistance and dyslipidemia were significantly correlated with the USS.
NAFLD was developed spontaneously among aging in rhesus monkeys (with increased prevalence in the MetS monkeys), which provided an ideal model for NAFLD. The newly developed USS system can be used to evaluate fatty liver in the rhesus monkey. The model as well as the noninvasive assessment methodology will provide a powerful tool for mechanistic studies and preclinical test of novel therapies for NAFLD.
非酒精性脂肪性肝病(NAFLD)是一种全球性流行病,影响着20%-30%的普通人群。目前可用的NAFLD动物模型与临床的相关性较低。在本研究中,我们旨在建立恒河猴NAFLD模型,并开发一种超声脂肪变性评分(USS)系统,用于对该模型中的肝脏脂肪变性进行分级。
我们对86只患有和未患有代谢综合征(MetS)的恒河猴进行了肝脏超声检查和血液生化检测,其中45只动物进一步接受了组织病理学分析。
恒河猴NAFLD的肝脏组织学特征与NAFLD患者相似。组织学脂肪变性分级与USS之间存在密切相关性(Spearman系数,0.705,p<0.001)。当截断值为USS2时,USS的敏感性为87.5%,特异性为94.6%。此外,USS2-3组中MetS的患病率显著更高。包括肥胖、胰岛素抵抗和血脂异常在内的多种心脏代谢疾病危险因素与USS显著相关。
恒河猴在衰老过程中自发发生NAFLD(在患有MetS的猴子中患病率更高),这为NAFLD提供了一个理想模型。新开发的USS系统可用于评估恒河猴的脂肪肝。该模型以及这种非侵入性评估方法将为NAFLD的机制研究和新疗法的临床前测试提供有力工具。