摘要
激酶活性异常或过度表达与包括肝纤维化在内的多种疾病的发生密切相关,已成为治疗这些疾病的重要药物靶点。蛋白激酶中的酪氨酸激酶和丝/苏氨酸以及脂类激酶中的磷脂酰肌醇-3激酶等能够通过调节肝星状细胞的活性及肝内血管生成等直接或间接机制参与肝纤维化的发生和发展。近期研究表明,小分子激酶抑制剂能够通过靶向激酶抑制细胞增殖以及血管生成从而发挥抗肝纤维化作用,有望为肝纤维化治疗提供一种新的治疗手段。本文对酪氨酸激酶、丝/苏氨酸激酶和磷脂酰肌醇-3激酶在肝纤维化中的作用和其参与调节肝纤维化发生发展的细胞信号通路,以及小分子激酶抑制剂在肝纤维化临床前动物模型和临床试验中的最新研究进展进行综述,为肝纤维化的治疗研究提供新的策略。
The aberrant activities or overexpression of kinases have been closely linked to the development of many diseases,including liver fibrosis,and kinases have become important therapeutic targets for these diseases.Protein kinases,including tyrosine kinases and serine/threonines protein kinases,and phosphoinositide 3-kinase(PI3K)are involved in the development of liver fibrosis through direct and indirect mechanisms,such as regulating the activation of hepatic stellate cells and intrahepatic angiogenesis.Recent studies have shown that small molecule kinase inhibitors(SMKIs)manifest great potential for treating liver fibrosis by inhibiting cell proliferation and angiogenesis.The present review summarizes the activities of tyrosine kinase,serine/threonine kinase and PI3K in liver fibrosis,as well as the pathway they involved in during the development of liver fibrosis,and the recently reported antifibrotic effects of various SMKIs both on preclinical animal models and on patients with liver fibrosis in clinical trials.
作者
赵莉梦
王淑珍
ZHAO Limeng;WANG Shuzhen(School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2018年第2期147-157,共11页
Journal of China Pharmaceutical University
