摘要
非酒精性脂肪性肝炎（NASH）曾经在全球范围内出现，而且有效的疗法，尤其是针对肝纤维化的疗法可以明显改善患者预后；日前来自日本的研究人员通过研究鉴别出了一种激素介导的机制，其或许能够限制纤维化相关的非酒精性脂肪性肝炎和肝硬化的发生。相关研究刊登于国际杂志Scientific Reports上，该研究或为后期开发相应疾病的新型疗法提供新的思路。
Hepatic fibrosis in nonalcoholic steatohepatitis (NASH) and cirrhosis determines patient prognosis; however, effective treatment for fibrosis has not been established. Oxidative stress and inflammation activate hepatic stellate cells (HSCs) and promote fibrosis. In contrast, cellular senescence inhibits HSCs’ activity and limits fibrosis. The aim of this study was to explore the effect of IGF-I on NASH and cirrhotic models and to clarify the underlying mechanisms. We demonstrate that IGF-I significantly ameliorated steatosis, inflammation, and fibrosis in a NASH model, methionine-choline-deficient diet-fed db/db mice and ameliorated fibrosis in cirrhotic model, dimethylnitrosamine-treated mice. As the underlying mechanisms, IGF-I improved oxidative stress and mitochondrial function in the liver. In addition, IGF-I receptor was strongly expressed in HSCs and IGF-I induced cellular senescence in HSCs in vitro and in vivo. Furthermore, in mice lacking the key senescence regulator p53, IGF-I did not induce cellular senescence in HSCs or show any effects on fibrosis. Taken together, these results indicate that IGF-I induces senescence of HSCs, inactivates these cells and limits fibrosis in a p53-dependent manner and that IGF-I may be applied to treat NASH and cirrhosis.
出处
《现代生物医学进展》
CAS
2017年第4期I0001-I0001,共1页
Progress in Modern Biomedicine
