Role of autophagy in liver diseases associated with stress

我们研究了慢性乙型肝炎(CHB)、慢性丙型肝炎(CHC)和非酒精性脂肪性肝病(NAFLD)患者肝细胞内质网(ER)应激，以及氧化应激、自噬与Mallory-Denk小体(MDB)形成的关系。我们用蛋白酶体抑制剂(PI)或游离脂肪酸(FFA)处理Huh7细胞，并用免疫印迹法检测内质网应激、泛素化蛋白和LC_3。PI或FFA处理可增加泛素化蛋白并激活自噬。CHC和NAFLD的样本显示，MDB位于氧化应激较强的区域，含有MDB的细胞减少了氧化应激。角蛋白8(K8)在CHC和NAFLD的MDB阳性细胞中呈强阳性表达。在慢性丙型肝炎和非酒精性脂肪肝患者中，由于氧化应激导致自噬增加，其转氨酶水平显著降低。这些结果表明，MDBS保护肝细胞免受氧化应激，自噬减少了肝脏损伤。

We investigated endoplasmic reticulum (ER) stress in hepatoma cells, and the relations between oxidative stress, autophagy and Mallory-Denk body (MDB) formation in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) or non-alcoholic fatty liver disease (NAFLD). We treated Huh7 cells with proteasome inhibitor (PI) or free fatty acid (FFA) and evaluated ER stress, ubiquitinated proteins and LC3with western blotting. Treatment with PI or FFA increased ubiquitinated proteins and activated autophagy. Samples of CHC and NAFLD showed MDBs in areas with strong oxidative stress and that the MDB-containing cells reduced oxidative stress. Keratin 8 (K8) expression was strong in MDB-containing cells in CHC and NAFLD. Aminotransferase values were significantly lower in patients with CHC and NAFLD in whom autophagy was increased in response to oxidative stress. These results suggest that MDBs protect hepatocytes from oxidative stress and that autophagy reduces hepatic damage.