膳食维生素 D 与肾功能正常的大鼠高磷诱导的心脏重塑相互作用。
Dietary vitamin D interacts with high phosphate-induced cardiac remodeling in rats with normal renal function.
机构信息
Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Nephrol Dial Transplant. 2020 Mar 1;35(3):411-421. doi: 10.1093/ndt/gfz156.
BACKGROUND
Vitamin D (VD) and phosphate (Pi) load are considered as contributors to cardiovascular disease in chronic kidney disease and the general population, but interactive effects of VD and Pi intake on the heart are not clearly illustrated.
METHODS
We fed normal male rats with three levels of dietary VD (100, 1100 or 5000 IU/kg chow) and Pi (0.2, 0.6 or 1.6%) (3X3 design) for 8 weeks and examined renal and cardiac function and histology.
RESULTS
High dietary Pi decreased plasma and renal Klotho and plasma 25-hydroxyvitamin D, and increased plasma Pi, fibroblast growth factor 23 and parathyroid hormone without affecting renal function, while low Pi increased plasma and renal Klotho. Both low and high VD diets enhanced high Pi-reduced Klotho expression. Low dietary VD reduced-plasma Klotho was rescued by a low Pi diet. High dietary Pi reduced-cardiac ejection fraction was not modified by a low or high VD diet, but the dietary VD effects on cardiac pathologic changes were more complex. High dietary Pi-induced cardiac hypertrophy was attenuated by a low VD and exacerbated by a high VD diet. In contrast, high dietary Pi -induced cardiac fibrosis was magnified by a low VD and attenuated by a high VD diet.
CONCLUSIONS
High Pi diet induces hypertrophy and fibrosis in left ventricles, a low VD diet accelerates high Pi-induced fibrosis, and a high VD diet exacerbated high Pi -induced hypertrophy. Therefore, cardiac phosphotoxicity is exacerbated by either high or low dietary VD in rats with normal kidney function.
背景
维生素 D（VD）和磷酸盐（Pi）负荷被认为是慢性肾脏病和普通人群心血管疾病的致病因素，但 VD 和 Pi 摄入对心脏的相互作用影响尚不清楚。
方法
我们用三种不同水平的膳食 VD（100、1100 或 5000 IU/kg 饲料）和 Pi（0.2、0.6 或 1.6%）（3X3 设计）喂养正常雄性大鼠 8 周，检测肾脏和心脏功能及组织学变化。
结果
高膳食 Pi 降低了血浆和肾脏 Klotho 及血浆 25-羟维生素 D，增加了血浆 Pi、成纤维细胞生长因子 23 和甲状旁腺激素，而不影响肾功能，而低 Pi 增加了血浆和肾脏 Klotho。低和高 VD 饮食均增强了高 Pi 降低的 Klotho 表达。低膳食 VD 降低的血浆 Klotho 可被低 Pi 饮食所挽救。高膳食 Pi 降低的心脏射血分数不受低或高 VD 饮食的影响，但 VD 对心脏病理变化的影响更为复杂。高膳食 Pi 诱导的心脏肥大被低 VD 饮食减弱，而被高 VD 饮食增强。相反，高膳食 Pi 诱导的心脏纤维化被低 VD 饮食放大，被高 VD 饮食减弱。
结论
高 Pi 饮食可引起左心室肥大和纤维化，低 VD 饮食加速高 Pi 诱导的纤维化，高 VD 饮食加重高 Pi 诱导的肥大。因此，在肾功能正常的大鼠中，高或低膳食 VD 均可加重心脏磷毒性。
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