The aim of this study was to explore biological interaction and pathophysiology mechanisms in a new mouse model of cardiovascular–kidney–metabolic (CKM) syndrome, induced by chronic moderate renal failure in combination with consumption of a customized Western diet rich in carbohydrates, fat and salt. Male C57BL/6J mice were subjected to unilateral nephrectomy, fed a customized Western diet rich not only in sugar and fat but also in salt, and followed for 12 weeks or 20 weeks. Sham-operated mice on a standard chow served as healthy controls. Body composition, weight gain, glucose metabolism, fat distribution, blood pressure, cardiac function, vascular reactivity, renal function, inflammation and mitochondrial function were measured and combined with biochemical and histopathological analyses. The novel triple-hit model of CKM syndrome showed signs and symptoms of metabolic syndrome, disturbed glucose metabolism, impaired adipocyte physiology and fat redistribution, cardiovascular dysfunction, renal damage and dysfunction, systemic inflammation, elevated blood pressure and cardiac remodeling. The pathological changes were more pronounced in mice after prolonged exposure for 20 weeks, but no deaths occurred. In the present mouse model of CKM syndrome, profound and significant metabolic, cardiac, vascular and renal dysfunctions and injuries emerged by using a Western diet rich not only in fat and carbohydrates but also in salt. This multisystem disease model could be used for mechanistic studies and the evaluation of new therapeutic strategies.

本研究的目的是探讨心血管-肾脏-代谢 （CKM） 综合征的新小鼠模型中的生物相互作用和病理生理学机制，该模型由慢性中度肾功能衰竭联合食用富含碳水化合物、脂肪和盐的定制西方饮食诱导。雄性 C57BL/6J 小鼠进行单侧肾切除术，喂食定制的西餐，不仅富含糖和脂肪，还富含盐，并随访 12 周或 20 周。在标准食物上进行的假手术小鼠作为健康对照。测量身体成分、体重增加、葡萄糖代谢、脂肪分布、血压、心功能、血管反应性、肾功能、炎症和线粒体功能，并结合生化和组织病理学分析。CKM 综合征的新型三重打击模型表现出代谢综合征、葡萄糖代谢紊乱、脂肪细胞生理和脂肪再分布受损、心血管功能障碍、肾损伤和功能障碍、全身炎症、血压升高和心脏重塑的体征和症状。小鼠长时间暴露 20 周后病理变化更明显，但未发生死亡。在目前的 CKM 综合征小鼠模型中，通过使用不仅富含脂肪和碳水化合物而且富含盐的西方饮食，出现了深刻而显着的代谢、心脏、血管和肾脏功能障碍和损伤。这种多系统疾病模型可用于机制研究和新治疗策略的评估。