SREBP/PCSK9通路与抗精神病药物所致脂代谢紊乱相关性的研究进展  

Research progress in the correlation between SREBP/PCSK9 pathway and lipid metabolism disorders induced by antipsychotics

作　　者：马家树 郑云哨[2] 孙丰霞[2] 樊运莉 范允明 苏现彪 王忠宝 翁柠 李然然 MA Jiashu;ZHENG Yunshao;SUN Fengxia;FAN Yunli;FAN Yunming;SU Xianbiao;WANG Zhongbao;WENG Ning;LI Ranran(School of Mental Health,Jining Medical University,Jining Shandong 272067;Department of Psychiatry,Shandong Mental Health Center,Jinan 250014;Department of Psychiatry,Shandong Daizhuang Hospital,Jining Shandong 272051,China)

机构地区：[1]济宁医学院精神卫生学院,山东济宁272067 [2]山东省精神卫生中心精神科,济南250014 [3]山东省戴庄医院精神科,山东济宁272051

出　　处：《中南大学学报（医学版）》2023年第10期1529-1538,共10页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(82101580);山东省中医药科技发展计划项目(2019-0528)。

摘　　要：抗精神病药物是治疗精神分裂症的主要药物,但其使用会导致脂代谢紊乱,从而增加患者发生心血管疾病的风险,缩短患者的预期寿命,并严重影响治疗的依从性。目前,抗精神病药物引起脂代谢紊乱的具体机制尚不清楚。固醇调节元件结合蛋白(sterol regulatory element binding protein,SREBP)是调控脂代谢的关键转录因子。前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)作为SREBP下游调控基因之一,对低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)具有重要的调控作用,是最近降脂药物研究的重要靶点。近期研究表明,抗精神病药物可以通过SREBP/PCSK9通路影响脂代谢。深入了解该通路在抗精神药物相关代谢异常中的作用机制将促进精神分裂症患者脂代谢紊乱的预防和新药的研发应用。Antipsychotic medications are commonly used to treat schizophrenia,but they can have negative effects on lipid metabolism,leading to an increased risk of cardiovascular diseases,reduced life expectancy,and difficulties with treatment adherence.The specific mechanisms by which antipsychotics disrupt lipid metabolism are not well understood.Sterol regulatory element-binding proteins(SREBPs)are important transcriptional factors that regulate lipid metabolism.Proprotein convertase subtilisin/kexin type 9(PCSK9),a gene regulated by SREBPs,plays a critical role in controlling levels of low-density lipoprotein cholesterol(LDL-C)and has become a focus of research on lipid-lowering drugs.Recent studies have shown that antipsychotic drugs can affect lipid metabolism through the SREBP/PCSK9 pathway.A deep understanding of the mechanism for this pathway in antipsychotic drug-related metabolic abnormalities will promote the prevention of lipid metabolism disorders in patients with schizophrenia and the development and application of new drugs.

关 键 词：抗精神病药物 固醇调节元件结合蛋白 前蛋白转化酶枯草溶菌素9 脂代谢紊乱 

分 类 号：R969[医药卫生—药理学]