Department of Ultrasound, Jinan Central Hospital of Shandong University, Shandong, China.
Department of Nephrology, Qilu Hospital of Shandong University, Shandong, China.
J Chin Med Assoc. 2018 Aug;81(8):691-698. doi: 10.1016/j.jcma.2018.01.010. Epub 2018 May 7.
Hypertension is a major global public health issue. Uncontrolled hypertension leads to organ damage, especially renal damage. Calcitriol is used to treat osteoporosis, promote bone formation, and increase bone mass. Previous studies have demonstrated that 1,25(OH)2D3, in addition to its classic role, also has multiple immune regulation and renoprotective functions and inhibits the activity of the renin-angiotensin-aldosterone system (RASS). The aim of the current study was to investigate the renoprotective effects of calcitriol in a spontaneously hypertensive rat (SHR) model.
A total of 18 SHRs and 8 age-matched normal Wistar rats were enrolled. SHRs were randomly divided into a hypertensive nephropathy group (H), a hypertensive nephropathy treated with calcitriol group (D) and a control group (NS). The rats were sacrificed after 16 weeks of treatment. The blood pressure (BP) of rats were measured one time every 4 weeks. The levels of serum albumin, serum creatinine, blood calcium, serum Vitamin D and 24-h urinary protein were measured after 16 weeks treatment. The protein level of WT1, nephrin and vitamin D receptor (VDR) was examined by Western blotting and immunohistochemical staining.
There were no notable changes in blood pressure or serum creatinine in group H and D compared with group NS. The albumin, calcium and vitamin D serum levels in group H were significantly decreased compared with group NS and significantly increased in group D compared with group H. The level of 24-h urine protein significantly increased in group H compared with group NS and significantly decreased in group D compared with group H. The expression of VDR, WT1 and nephrin in the kidney were all significantly decreased in group H compared with group NS and significantly increased in group D compared with group H.
The present results indicated that there was injury of podocytes in hypertensive nephropathy, which can be ameliorated by calcitriol in SHR, but there was no significant anti-hypertensive effect. Vitamin D/VDR decreased proteinuria perhaps by increasing expression of nephrin and WT1 protein in podocyte of SHRs.
高血压是一个全球性的主要公共卫生问题。未得到控制的高血压会导致器官损伤，特别是肾脏损伤。骨化三醇用于治疗骨质疏松症，促进骨形成，增加骨量。先前的研究表明，1,25（OH）2D3 除了其经典作用外，还具有多种免疫调节和肾保护功能，并抑制肾素-血管紧张素-醛固酮系统（RASS）的活性。本研究旨在探讨骨化三醇在自发性高血压大鼠（SHR）模型中的肾保护作用。
共纳入 18 只 SHR 和 8 只年龄匹配的正常 Wistar 大鼠。SHR 随机分为高血压肾病组（H）、骨化三醇治疗高血压肾病组（D）和对照组（NS）。治疗 16 周后处死大鼠。每 4 周测量一次大鼠血压。治疗 16 周后测量血清白蛋白、血清肌酐、血钙、血清维生素 D 和 24 小时尿蛋白水平。通过 Western blot 和免疫组织化学染色检测 WT1、nephrin 和维生素 D 受体（VDR）的蛋白水平。
与 NS 组相比，H 组和 D 组的血压或血清肌酐无明显变化。与 NS 组相比，H 组血清白蛋白、钙和维生素 D 水平明显降低，D 组明显升高。与 NS 组相比，H 组 24 小时尿蛋白水平显著升高，D 组显著降低。与 NS 组相比，H 组肾脏中 VDR、WT1 和 nephrin 的表达均显著降低，D 组显著升高。
本研究结果表明，高血压肾病存在足细胞损伤，骨化三醇可改善 SHR 的损伤，但无明显降压作用。维生素 D/VDR 通过增加 SHR 足细胞中 nephrin 和 WT1 蛋白的表达减少蛋白尿。
