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凋亡信号调节激酶-1抑制剂在非酒精性脂肪性肝炎中的研究进展
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引用本文:韩磊,张小猛,全旭,雷永华,钱海.凋亡信号调节激酶-1抑制剂在非酒精性脂肪性肝炎中的研究进展[J].中国药科大学学报,2019,50(2):135-142.
Cite:HAN Lei,ZHANG Xiaomeng,QUAN Xu,LEI Yonghua,QIAN Hai.Research progress of apoptosis signal regulating kinases-1 and its inhibitors in non-alcoholic steatohepatitis[J].J China Pharm Univ,2019,50(2):135-142.
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作者单位
韩磊 中国药科大学新药研究中心南京圣和药业股份有限公司 
张小猛 南京圣和药业股份有限公司 
全旭 南京圣和药业股份有限公司 
雷永华 南京圣和药业股份有限公司 
钱海 中国药科大学新药研究中心 
基金项目:国家自然科学基金资助项目(No.81673299)
中文摘要:非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)是最常见的慢性肝病,当前未见有效疗法。凋亡信号调节激酶-1(apoptosis signal regulating kinases 1,ASK-1)是细胞丝裂原活化蛋白激酶激酶激酶(mitogen-activated protein kinase kinase kinases,MAPKKKs)家族成员之一,当机体受到细胞内活性氧簇应激、内质网应激、钙内流和细胞外炎症等信号刺激时,ASK-1激活c-Jun氨基末端激酶(c-Jun amino terminal kinasec,JNK)和p38 MAPK通路,从而促进细胞增殖、分化、凋亡以及炎症因子的产生,诱发NASH、纤维化等疾病,因此可通过抑制ASK-1的活性来治疗NASH。本文对当前NASH的治疗手段、ASK-1结构和作用机制以及近年ASK-1抑制剂治疗NASH的研究进展进行综述,旨在为该类抑制剂的设计与开发提供参考。
中文关键词:ASK-1抑制剂  非酒精性脂肪性肝炎  凋亡信号调节激酶-1  进展
 
Research progress of apoptosis signal regulating kinases-1 and its inhibitors in non-alcoholic steatohepatitis
Abstract:Non-alcoholic steatohepatitis(NASH)is the most common chronic liver disease. However, the treatment of NASH remains challenging. Apoptosis signal regulating kinases-1(ASK-1)is a member of mitogen-activated protein kinase kinase kinases(MAPKKKs). When the body is stimulated by reactive oxygen species, endoplasmic reticulum stress, calcium influx and extracellular inflammatory signals, c-Jun amino terminal kinases(JNK)and p38 MAPK wiube activated, which then promotes cell proliferation, differentiation, apoptosis and production of inflammatory factors, and causes NASH, fibrosis and other diseases. Therefore, ASK-1 inhibitors can be used to treat NASH. This paper reviews the current treatment methods of NASH, the structure and mechanism of ASK-1, and the research progress of ASK-1 inhibitors in the treatment of NASH in recent years, which aims to explore the guiding significance for the design and development of ASK-1 inhibitors.
keywords:ASK-1 inhibitors  non-alcoholic steatohepatitis  apoptosis signal regulating kinases-1  advances
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