Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Biochem Biophys Res Commun. 2010 Jan 22;391(4):1731-6. doi: 10.1016/j.bbrc.2009.12.144. Epub 2009 Dec 31.
Non-alcoholic steatohepatitis (NASH) develops in a subset of patients with non-alcoholic fatty liver disease (NAFLD), but the exact mechanisms involved in the progression of NAFLD to NASH remain poorly understood. We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the apoptosis of hepatocytes that is related to the severity of NASH. We separated primary hepatocytes from the NAFLD liver caused by a high-fat diet. The production of intracellular reactive oxygen species was increased in steatotic hepatocytes, which were also sensitive to TNF-alpha. This factor induced significant apoptosis through the signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) pathway. We describe here a novel culture model of steatotic hepatocytes separated from the NAFLD liver, and demonstrate that TNF-alpha induces their apoptosis in vitro.
非酒精性脂肪性肝炎 (NASH) 发生于非酒精性脂肪性肝病 (NAFLD) 患者中的一部分亚群中，但 NAFLD 向 NASH 进展的确切机制仍知之甚少。我们研究了肿瘤坏死因子-α (TNF-α) 在与 NASH 严重程度相关的肝细胞凋亡中的作用。我们从高脂肪饮食引起的 NAFLD 肝脏中分离出原代肝细胞。脂肪变性肝细胞内活性氧的产生增加，且对 TNF-α敏感。该因子通过信号调节激酶 1 (ASK1) 和 c-Jun N 端激酶 (JNK) 途径诱导明显的细胞凋亡。我们在这里描述了一种从 NAFLD 肝脏中分离出脂肪变性肝细胞的新型培养模型，并证明 TNF-α在体外诱导其凋亡。
