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食品补充剂Flexovital对小鼠心血管-肾脏-代谢综合征模型的保护作用。

Protective Effects of the Food Supplement Flexovital in a Model of Cardiovascular-Kidney-Metabolic Syndrome in Mice.

作者信息

Carvalho Lucas Rannier Ribeiro Antonino, Tydén Maria, Shimari Miho, Zhuge Zhengbing, Schiffer Tomas A, de Oliveira Monteiro Matheus Morais, Lundberg Jon O, Weitzberg Eddie, Andersson Daniel C, Fellström Bengt, Carlström Mattias

机构信息

Department of Physiology and Pharmacology, Karolinska Institutet, 17165 Solna, Sweden.

Department of Medical Sciences, Nephrology, Uppsala University, 75236 Uppsala, Sweden.

出版信息

Nutrients. 2024 Nov 28;16(23):4105. doi: 10.3390/nu16234105.

Abstract

The prevalence of cardiovascular-kidney-metabolic (CKM) syndrome is increasing rapidly, and cardiovascular complications pose significant risks in individuals with kidney disease and metabolic dysfunction. Understanding the mechanisms of CKM disorders is crucial, as is the discovery of novel preventive treatments. This study aimed to examine the therapeutic effects of a specially formulated nitric oxide-enhancing food additive in a mouse model of CKM syndrome induced by unilateral nephrectomy (UNX) in combination with chronic Western diet (WD) feeding. : C57BL/6J mice underwent UNX and were fed a WD high in salt, sugar, and fat for 12 weeks, compared to sham-operated mice on standard chow. One group of UNX+WD mice received Flexovital (FLX), a food additive containing extracts of and beetroot, and the amino acids L-arginine and L-citrulline. CKM parameters were assessed both in vivo and ex vivo alongside histological and biochemical analyses. : The UNX+WD mice showed an increase in body fat mass, the fat/lean mass ratio, and adipocyte area, of which most were significantly reduced by FLX. Elevated fasting glucose levels were also reduced by FLX, which tended towards improving glucose clearance. Elevated arterial blood pressure and endothelial dysfunction in UNX+WD mice were significantly reduced by FLX. FLX improved GFR and reduced glomerular and tubular injuries in UNX+WD mice. Additionally, FLX increased the P/O ratios of oxidative phosphorylation in the isolated renal mitochondria of UNX+WD mice. : In this model of CKM syndrome, FLX effectively prevented the onset and progression of CKM dysfunctions induced by UNX+WD, as well as the associated organ injuries. These promising results highlight the need for validation in upcoming human trials.

摘要

心血管-肾脏-代谢(CKM)综合征的患病率正在迅速上升,心血管并发症对患有肾脏疾病和代谢功能障碍的个体构成重大风险。了解CKM疾病的机制至关重要,发现新的预防性治疗方法同样重要。本研究旨在研究一种特殊配方的一氧化氮增强型食品添加剂在单侧肾切除(UNX)联合慢性西方饮食(WD)喂养诱导的CKM综合征小鼠模型中的治疗效果。方法:将C57BL/6J小鼠进行UNX手术,并给予高盐、高糖和高脂肪的WD饲料喂养12周,与接受假手术并喂食标准饲料的小鼠进行比较。一组UNX+WD小鼠接受Flexovital(FLX),这是一种含有[具体成分]提取物、甜菜根以及氨基酸L-精氨酸和L-瓜氨酸的食品添加剂。在体内和体外评估CKM参数,并进行组织学和生化分析。结果:UNX+WD小鼠的体脂质量、脂肪/瘦体重比和脂肪细胞面积增加,而FLX可使其中大部分显著降低。FLX还降低了升高的空腹血糖水平,倾向于改善葡萄糖清除率。FLX显著降低了UNX+WD小鼠升高的动脉血压和内皮功能障碍。FLX改善了UNX+WD小鼠的肾小球滤过率(GFR),并减少了肾小球和肾小管损伤。此外,FLX增加了UNX+WD小鼠分离的肾线粒体中氧化磷酸化的P/O比值。结论:在该CKM综合征模型中,FLX有效预防了UNX+WD诱导的CKM功能障碍的发生和进展以及相关器官损伤。这些有前景的结果凸显了在即将进行的人体试验中进行验证的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d512/11643529/eb2d37fbe480/nutrients-16-04105-g001.jpg

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