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链脲佐菌素诱导的非酒精性脂肪性肝炎小鼠经钆塞酸二钠增强磁共振成像后的自然病程:与单纯性脂肪肝小鼠的比较

The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: Comparison with simple steatosis mice.

作者信息

Akai Hiroyuki, Kiryu Shigeru, Ohta Yasunori, Yasaka Koichiro, Nakano Yoshiyasu, Inoue Yusuke, Ohtomo Kuni

机构信息

Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

出版信息

Magn Reson Imaging. 2017 May;38:123-128. doi: 10.1016/j.mri.2016.12.027. Epub 2017 Jan 3.

Abstract

PURPOSE

To clarify the development of HCC, temporal change of steatosis and Gd-EOB-DTPA enhancement of non-alcoholic steatohepatitis (NASH) model mice by magnetic resonance imaging (MRI).

MATERIALS AND METHODS

All animal experiments were approved by the institution's Animal Research Committee. MRI was performed on six NASH and six simple steatosis (SS) model mice every 2weeks from the ages of 8weeks to 16weeks. The sequential changes in the number and size of the focal liver lesions detected on Gd-EOB-DTPA-enhanced MRI were evaluated. Additionally, the hepatic fat fraction (HFF), contrast-to-noise ratio (CNR) and relative enhancement (RE) were calculated at each time point. The temporal changes and correlations in these parameters were evaluated.

RESULTS

All alive NASH model mice demonstrated focal liver lesions from week 10, at the latest. Number of the lesions increased with time, and all the lesion enlarged with time. All the lesions larger than 1mm were confirmed as hepatocellular carcinoma (HCC) pathologically. While the HFF remained constant in NASH model mice, HFF in SS model mice dramatically increased with time. CNR of the NASH model mice remained constant through the study period, while CNR in SS model mice decreased with time. Although no correlation was seen in NASH model mice, the HFF showed a negative correlation against CNR and RE in SS model mice.

CONCLUSION

Development of HCC was observed using Gd-EOB-DTPA-enhanced MRI only in NASH model mice. Degree of steatosis and hepatic enhancement by Gd-EOB-DTPA was both constant in NASH model mice, while steatosis increased and hepatic enhancement decreased with time in SS model mice.

摘要

目的

通过磁共振成像(MRI)明确非酒精性脂肪性肝炎(NASH)模型小鼠肝癌(HCC)的发生发展、脂肪变性的时间变化以及钆塞酸二钠(Gd-EOB-DTPA)增强情况。

材料与方法

所有动物实验均经机构动物研究委员会批准。从8周龄至16周龄,每2周对6只NASH模型小鼠和6只单纯性脂肪变性(SS)模型小鼠进行MRI检查。评估钆塞酸二钠增强MRI检测到的局灶性肝损伤数量和大小的连续变化。此外,在每个时间点计算肝脏脂肪分数(HFF)、对比噪声比(CNR)和相对增强(RE)。评估这些参数的时间变化及相关性。

结果

所有存活的NASH模型小鼠最晚在第10周出现局灶性肝损伤。损伤数量随时间增加,所有损伤均随时间增大。所有直径大于1mm的损伤经病理证实为肝细胞癌(HCC)。NASH模型小鼠的HFF保持恒定,而SS模型小鼠的HFF随时间显著增加。NASH模型小鼠的CNR在研究期间保持恒定,而SS模型小鼠的CNR随时间下降。虽然在NASH模型小鼠中未观察到相关性,但在SS模型小鼠中HFF与CNR和RE呈负相关。

结论

仅在NASH模型小鼠中使用钆塞酸二钠增强MRI观察到了HCC的发生发展。NASH模型小鼠的脂肪变性程度和钆塞酸二钠增强的肝脏均保持恒定,而SS模型小鼠的脂肪变性随时间增加,肝脏增强随时间下降。

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