摘要
前蛋白转化酶枯草溶菌素9(PCSK9)是一种主要由肝脏合成的丝氨酸蛋白酶,在胃肠道、胰腺、肾脏和中枢神经系统中也有表达。PCSK9参与脂质代谢调节的肝细胞内外分子靶点众多,在肝脏中主要通过与肝细胞膜表面低密度脂蛋白受体(LDLR)结合靶向溶酶体降解,升高血浆低密度脂蛋白胆固醇水平。既往PCSK9在家族性遗传性高胆固醇血症、动脉粥样硬化、心肌梗死、肿瘤等疾病中得到广泛关注,并促进PCSK9抑制剂的快速研发,在治疗高胆固醇血症、降低心血管疾病风险中发挥重要作用。随着PCSK9研究的深入及慢性肝病发病率的逐渐提高,PCSK9与慢性肝病发生发展的关系也逐渐被揭示。基于上述背景,本文阐述PCSK9在多种临床常见慢性肝脏疾病(酒精性肝病、非酒精性脂肪肝、非酒精性脂肪性肝炎、病毒性肝炎以及肝癌)中所发挥的作用,以期为慢性肝脏疾病的临床诊疗提供新思路。
Proprotein convertase subtilisin/kexin type 9(PCSK9)is a serine protease predominantly synthesized by the liver,with expression also found in the gastrointestinal tract,pancreas,kidneys,and central nervous system.PCSK9 is involved in regulating lipid metabolism with numerous molecular targets both inside and outside hepatocytes.In the liver,it mainly targets lysosomal degradation through binding to lowdensity lipoprotein receptor(LDLR)on the cell membrane surface,thereby increasing plasma levels of low-density lipoprotein cholesterol.PCSK9 has garnered widespread attention in familial hypercholesterolemia,atherosclerosis,myocardial infarction,cancer,and other diseases,which has accelerated the rapid development of PCSK9 inhibitors,and played a significant role in the treatment of hypercholesterolemia and reducing the risk of cardiovascular diseases.As research on PCSK9 deepens and the prevalence of chronic liver diseases increases,the relationship between PCSK9 and the development of chronic liver diseases is gradually being revealed.Given the aforementioned background,this article elaborates on the role of PCSK9 in various common chronic liver diseases in clinical practice,including alcoholic liver disease,non-alcoholic fatty liver disease,non-alcoholic steatohepatitis,viral hepatitis,and liver cancer,aiming to offer new perspectives for the clinical diagnosis and treatment of chronic liver diseases.
作者
方开晗
彭秀达
费书珂
FANG Kaihan;PENG Xiuda;FEI Shuke(Department of Hepatobiliary Pancreatic and Splenic Surgery,the Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang,Hunan 421001,China)
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2024年第1期114-121,共8页
China Journal of General Surgery
基金
湖南省教育厅研究生科研创新基金资助项目(CX20231005)
湖南省自然科学基金资助项目(2023JJ60354)
湖南省科技厅临床医疗技术创新引导基金资助项目(2021SK51701)。
关键词
肝疾病
前蛋白转化酶9
脂类代谢
综述
Liver Diseases
Proprotein Convertase 9
Lipid Metabolism
Review
