非酒精性脂肪性肝炎治疗靶点和靶向药物研发进展

Therapeutic targets and targeted drug development for non-alcoholic steatohepatitis

介绍了治疗非酒精性脂肪性肝炎的相关靶点和靶向药物研发方面的进展,分别简述了过氧化物酶体增殖物激活受体、乙酰辅酶A羧化酶、胰高血糖素样肽-1、甲状腺激素受体β、法尼醇X受体、成纤维细胞生长因子19/21、凋亡信号调节激酶1和C-C趋化因子受体2/5等多种非酒精性脂肪性肝炎治疗新靶点,分析了靶点相关药物及其在治疗非酒精性脂肪性肝炎的研发进展及其优缺点。分析表明,通过探索非酒精性脂肪性肝炎的相关靶点及研发的靶向药物,有助于解除非酒精性脂肪性肝炎给人类健康带来的巨大威胁。基于此,对其发展前景进行展望,指出今后可以在以下方面对治疗非酒精性脂肪性肝炎进行深入研究:1)找到非酒精性脂肪性肝炎主要致病机理,从源头治疗非酒精性脂肪性肝炎;2)针对非酒精性脂肪性肝炎的不同靶点进行药物联合治疗;3)研发新的治疗技术(基因疗法、核酸药物以及抗体偶联药物等),将其应用到非酒精性脂肪性肝炎治疗领域。

The progress in the development of relevant targets and targeted drugs for the treatment of non-alcoholic steatohepatitis(NASH)was presented,and various NASH targets such as peroxisome proliferator-activated receptors,acetyl CoA carboxylase,glucagon-like peptide-1,thyroid hormone receptorβ,farnesoid X receptor,fibroblast growth factor receptor 19 and 21,apoptosis signal-regulating kinase-1,C-C chemokine receptor types 2 and 5,respectively,were briefly described.The research progress,advantages and disadvantages of target-related drugs in the treatment of NASH were analyzed.The analysis shows that the great threat to human health posed by NASH can be solved by exploring the relevant targets of NASH and developing targeted drugs.Based on this,the prospect of its development is prospected,and it is pointed out that in-depth research on the treatment of NASH can be conducted in the following aspects:1)identifying the main pathogenic mechanism of NASH and treating NASH at the source;2)drug combination therapy for different targets of NASH;3)developing new therapeutic technologies such as gene therapy,nucleic acid drugs,and antibody-coupled drugs for the treatment of NASH.