FGF21类似物治疗动脉粥样硬化机制研究进展

动脉粥样硬化是冠心病、脑梗死、外周血管病的主要诱因，近年来发病率越来越高，严重威胁着人类生命健康。脂质代谢障碍是动脉粥样硬化的病理基础。成纤维细胞生长因子21(FGF21)是FGF家族的一种内分泌因子，它能够增加葡萄糖的摄取，调节脂质代谢，并使代谢活跃的器官（如肝脏和脂肪组织）中胰岛素反应敏感。FGF21水平与动脉粥样硬化的发生率和严重程度密切相关。然而，FGF21原型在血浆的半衰期短、体外易聚集，严重限制了其临床应用。近年来，对FGF21类似物的研究取得了突破性进展。综述了FGF21的生理作用，并讨论了基于FGF21类似物治疗动脉粥样硬化的主要突破和局限性，为FGF21蛋白类新药的开发提供了理论依据。

Mechanism Progress on Fibroblast Growth Factor 21 Analogue Treating Atherosclerosis

Atherosclerosis is the main cause of coronary heart disease, cerebral infarction and peripheral vascular disease. Incidence is increasing, which threatens human life and health seriously. Lipid metabolism disorder is the pathological basis of atherosclerosis. Fibroblast growth factor 21 (FGF21) is an endocrine factor of the FGF family. It increases glucose uptake, modulates lipid metabolism, and sensitizes insulin response in metabolically active organs, including the liver and adipose tissue. Emerging evidence showed a strong correlation between circulating FGF21 levels and the incidence and severity of atherosclerosis. However, the short plasma half-life of native FGF21 and its propensity to aggregate in vitro have limited its clinical application. Recently, breakthrough progress has been made in FGF21 analogues. The present review summarized the physiological roles of FGF21, and discussed major breakthroughs and limitations of FGF21 mimetic-based therapeutic strategies for treating atherosclerosis, which was expected to provide theoretical basis for the development of new FGF21 protein drugs.