Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Department of Anatomy and Embryology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.
Eur J Nutr. 2021 Feb;60(1):299-316. doi: 10.1007/s00394-020-02249-6. Epub 2020 Apr 22.
The study aimed to investigate the potential nephroprotective effects of vitamin D3 in metabolic syndrome (MetS) and the molecular basis of the underlying mechanisms of its action.
MetS was induced in adult male Wistar rats by adding fructose (10%) to every day drinking water and salt (3%) to the diet. Six weeks after fructose/salt consumption, fasting serum lipid profile and uric acid levels were determined, an oral glucose tolerance test (OGTT) was performed and kidney function was checked. MetS rats were then treated orally with vitamin D3 (10 µg/kg/day) for 6 weeks. At the end of the study period (12 weeks), the OGTT test was reperformed, anthropometrical parameters were measured, urine, blood and tissue samples were collected and the animals were euthanised.
The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia and impaired glucose tolerance. After 12 weeks, MetS rats displayed markedly declined renal function alongside with extravagant renal histopathological damages and interstitial fibrosis. Furthermore, significantly enhanced renal oxidative stress and inflammation were manifested. Vitamin D3 supplementation in MetS rats significantly reversed all the above-mentioned deleterious effects.
The study has indeed provided mounting evidence of the promising therapeutic potential of vitamin D3 against development and progression of MetS-induced nephropathy. A new insight has been introduced into the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5'adenosine monophosphate-activated protein kinase activation in the renoprotective effects of vitamin D3.
本研究旨在探讨维生素 D3 对代谢综合征(MetS)的潜在肾脏保护作用及其作用机制的分子基础。
通过在日常饮用水中添加果糖(10%)和饮食中添加盐(3%),在成年雄性 Wistar 大鼠中诱导 MetS。果糖/盐摄入 6 周后,测定空腹血清脂质谱和尿酸水平,进行口服葡萄糖耐量试验(OGTT),并检查肾功能。然后,MetS 大鼠口服给予维生素 D3(10μg/kg/天)治疗 6 周。在研究结束时(12 周),再次进行 OGTT 测试,测量人体测量参数,收集尿液、血液和组织样本,然后处死动物。
果糖/盐摄入 6 周后,MetS 的发生率得到确认,此时大鼠体重明显增加,表现为血脂异常、高尿酸血症、胰岛素抵抗、高胰岛素血症和葡萄糖耐量受损。12 周后,MetS 大鼠的肾功能明显下降,同时伴有明显的肾脏组织病理学损伤和间质纤维化。此外,还表现出明显增强的肾氧化应激和炎症。维生素 D3 补充剂可显著逆转 MetS 大鼠的所有上述有害作用。
该研究确实为维生素 D3 治疗 MetS 相关性肾病的潜在治疗潜力提供了充分的证据。研究引入了一个新的见解,即二肽基肽酶-4 抑制和 Sirtuin-1/5'腺苷单磷酸激活蛋白激酶的激活在维生素 D3 的肾脏保护作用中具有重要作用。