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载脂蛋白E基因敲除小鼠中的25-羟基维生素D-1-α-羟化酶:保护血管平滑肌细胞免于钙化的作用

25-Hydroxyvitamin D-1-α-hydroxylase in apoliporotein E knockout mice: The role of protecting vascular smooth muscle cell from calcification.

作者信息

Xiang Wei, Liao Wang, Yi Zhuwen, He Xiaojie, Ding Yan

机构信息

Department of Pediatrics, Hainan General Hospital, Haikou 570102, China; Department of Pediatrics, Maternal and Child Health care Hospital of Hainan Province, Haikou 570206, China.

Department of Cardiology, Hainan General Hospital, Haikou 570102, China.

出版信息

Biomed Pharmacother. 2017 Apr;88:971-977. doi: 10.1016/j.biopha.2017.01.093. Epub 2017 Feb 6.

DOI:10.1016/j.biopha.2017.01.093
PMID:28178628
Abstract

Previous publications widely reported that 25-hydroxyvitamin D-1-α-hydroxylase (CYP27B1) regulated the metabolism of 25-hydroxyvitamin D3, which has a close association between altered activity of vitamin D and vascular calcification has been reported in various human diseases, including chronic kidney disease, osteoporosis and atherosclerosis. Vascular calcification is a clinically significant component of atherosclerosis and may be promoted by ROS associated inflammatory. In this study, we evaluated the effect of 25-hydroxyvitamin D-1-α-hydroxylase on the atherosclerosis disease both in apolipoprotein (apo) E-/- mice and wild-type mice. We also isolated endothelial cell (ECs) and vascular smooth muscle cells (VSMCs) in aortic from the wild type mice and apoE-/- mice respectively, then investigated that after parathyroid hormone (PTH) both of the CYP27B1 and vitamin D receptor (VDR) expressions in apoE-/-EC and apoE-/-VSMC were higher than the wide-type EC and VSMCs. However, the increased proliferation and decreased apoptosis have showed in EC and VSMC compared with the cells from apo E-/- mice. Moreover, the index associated with vascular calcification such as intracellular Ca concentration and alkaline phosphatase (ALP) activity have been tested and the result suggested that the levels of the former index have improved in the apoE-/-EC and apoE-/-VSMC. We got similar conclusions under the pre-treatment with 1, 25(OH) 2D3.

摘要

以往的文献广泛报道,25-羟基维生素D-1-α-羟化酶(CYP27B1)调节25-羟基维生素D3的代谢,在包括慢性肾病、骨质疏松症和动脉粥样硬化在内的各种人类疾病中,维生素D活性改变与血管钙化之间存在密切关联。血管钙化是动脉粥样硬化的一个具有临床意义的组成部分,可能由活性氧相关炎症促进。在本研究中,我们评估了25-羟基维生素D-1-α-羟化酶对载脂蛋白E基因敲除(apo)E-/-小鼠和野生型小鼠动脉粥样硬化疾病的影响。我们还分别从野生型小鼠和apoE-/-小鼠的主动脉中分离出内皮细胞(ECs)和血管平滑肌细胞(VSMCs),然后研究发现,甲状旁腺激素(PTH)作用后,apoE-/-内皮细胞和apoE-/-血管平滑肌细胞中CYP27B1和维生素D受体(VDR)的表达均高于野生型内皮细胞和平滑肌细胞。然而,与apo E-/-小鼠的细胞相比,内皮细胞和平滑肌细胞中出现了增殖增加和凋亡减少的情况。此外,还检测了与血管钙化相关的指标,如细胞内钙浓度和碱性磷酸酶(ALP)活性,结果表明,apoE-/-内皮细胞和apoE-/-血管平滑肌细胞中前一项指标的水平有所改善。在1,25(OH)2D3预处理下,我们得出了类似的结论。

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