Wang Lulu, Wu Susu, Cai Minxuan, Ma Ji, Li Shengcun, Li Maoru, Xu Yan, Wei Lixin, Shang Jing
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China.
Int J Mol Sci. 2017 Aug 18;18(8):1681. doi: 10.3390/ijms18081681.
Because of the absence of the time course of histological nonalcoholic fatty hepatitis with subsequent fibrotic progression, the effective approaches available for controlling the onset and progression of non-alcoholic steatohepatitis (NASH) remain limited. Therefore, we detected the serum and liver tissue related lipid metabolism disorder, liver pathology and relative molecular makers alteration dynamically in a high fat-sucrose diet during different time points. High fat-sucrose diet significantly increased the serum lipid level on day 10. The excess lipid accumulation in liver was referred to as simple steatosis after the feeding of a high fat-sucrose diet for 20 days. The high fat-sucrose diet induced a hepatic inflammation response on day 30. Similarly, hepatic fibrosis was also initiated on day 30 and gradually formed from the 30th to the 50th day. Oxidative stress may be related with the process from NASH to liver fibrosis. Insulin resistance was involved in the progression from hepatic steatosis to NASH with hepatic fibrosis from the 20th to the 50th day. In conclusion, we established a high fat-sucrose diet induced nonalcoholic fatty hepatitis with liver fibrosis rat model, which presented the time course of histological nonalcoholic steatohepatitis and the initiation and progression change of characteristic molecular makers in the process from steatosis to hepatic fibrosis.
由于缺乏组织学上非酒精性脂肪性肝炎及其随后纤维化进展的时间进程，目前可用于控制非酒精性脂肪性肝炎（NASH）发病和进展的有效方法仍然有限。因此，我们在高脂高糖饮食的不同时间点动态检测血清和肝组织相关脂质代谢紊乱、肝脏病理学以及相关分子标志物的变化。高脂高糖饮食在第10天时显著提高了血清脂质水平。在高脂高糖饮食喂养20天后，肝脏中过量的脂质积累被称为单纯性脂肪变性。高脂高糖饮食在第30天时诱导了肝脏炎症反应。同样，肝纤维化也在第30天开始，并在第30天至第50天逐渐形成。氧化应激可能与从NASH到肝纤维化的过程有关。从第20天到第50天，胰岛素抵抗参与了从肝脂肪变性到NASH伴肝纤维化的进展过程。总之，我们建立了一种高脂高糖饮食诱导的非酒精性脂肪性肝炎伴肝纤维化大鼠模型，该模型呈现了组织学非酒精性脂肪性肝炎的时间进程以及从脂肪变性到肝纤维化过程中特征性分子标志物的起始和进展变化。
