基因敲除动脉粥样硬化小鼠模型研究进展

基因敲除小鼠动脉粥样硬化模型是目前较为认可的探讨动脉粥样硬化发病机制及寻找新药物靶点的关键工具,也应用于潜在抗动脉粥样硬化药物的药理和毒理研究。载脂蛋白E(ApoE)、低密度脂蛋白受体(LDLR)和B类Ⅰ型清道夫受体(SR-B1)等基因的表达促进机体脂质、胆固醇和低密度脂蛋白等转运和代谢,维持血管正常功能,敲除这些基因会引起脂质转运及代谢紊乱从而诱发动脉粥样硬化及并发症的发生发展。常见的基因敲除小鼠有ApoE基因敲除、LDLR基因敲除及其改良品系,这些模型小鼠能够客观反映敲除基因对动脉粥样硬化发生的影响,且广泛应用于动脉粥样硬化的非临床研究。本文阐述了当前基因敲除小鼠动脉粥样硬化模型的机制、应用和优缺点,以期为动脉粥样硬化发病机制研究及抗动脉粥样硬化药物筛选提供参考。

Advances in transgenic mouse model of atherosclerosis

The gene knockout mouse models of atherosclerosis are currently recognized as pivotal tools for exploring the different pathogenesis of atherosclerosis and novel drug targets, as well as for pharmacological and toxicological studies of potential anti-atherosclerotic drugs. The expressions of apolipoprotein E(ApoE), low-density lipoprotein receptor(LDLR), scavenger receptor class B type Ⅰ(SR-B1) and other genes promotes the transport and metabolism of body lipids, cholesterol, low-density lipoprotein, etc., while maintaining normal vascular function. Knocking out these genes can trigger lipid transport and metabolic disorders, thereby inducing the onset and development of atherosclerosis as well as associated complications. Common knockout mice include ApoE-/-, LDLR-/-and its improved strains. These model mice can objectively reflect the effect of knockout genes on atherosclerosis and are widely used in atherosclerosis pathogenesis and preclinical studies. In this paper, the mechanisms,applications, advantages and disadvantages of current atherosclerosis gene knockout mouse models are described. Hopefully, it can provide reference for the study of the pathogenesis of atherosclerosis and the screening of anti-atherosclerosis drugs.