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体外血管钙化的化学和激素决定因素

Chemical and hormonal determinants of vascular calcification in vitro.

作者信息

Lomashvili K, Garg P, O'Neill W C

机构信息

Department of Medicine, Renal Division, Emory University, Georgia 30322, USA.

出版信息

Kidney Int. 2006 Apr;69(8):1464-70. doi: 10.1038/sj.ki.5000297.

DOI:10.1038/sj.ki.5000297
PMID:16531981
Abstract

Vascular calcification is a complex process that is dependent not only on the physicochemical effects of Ca, PO(4), and pH, but also on smooth muscle factors that may be regulated by these ions as well as by 1,25-dihydroxyvitamin D(3) (calcitriol) and parathyroid hormone (PTH). These minerals and hormones were tested in a model of medial calcification in rat aorta maintained in culture for 9 days. Calcification was quantitated as incorporation of (45)Ca, alkaline phosphatase activity was measured in aortic homogenates, and osteopontin production was measured from immunoblots of culture medium. At 1.8 mM Ca (1.46 mM free), calcification occurred at or above 2.8 mM PO(4). At 3.8 mM PO(4), calcification occurred at or above 1.10 mM free [Ca]. At a constant [Ca] x [PO(4)], calcification varied directly with [Ca] and inversely with [PO(4)]. Calcification was directly related to pH between 7.19 and 7.50 but not altered by PTH or calcitriol. Alkaline phosphatase activity and osteopontin production were increased by Ca, PO(4), calcitriol, and PTH. We conclude that calcification of rat aorta in vitro requires elevation of both [Ca] and [PO(4)], and that [Ca] rather than [PO(4)] or the product of the two is the dominant determinant. The induction of alkaline phosphatase and osteopontin indicates that Ca and PO(4) have effects in addition to simple physicochemical actions. Although PTH and calcitriol did not increase calcification in vivo, they have effects on smooth muscle that could influence calcification in vivo. Calcification is enhanced by alkalinity within the range produced during hemodialysis.

摘要

血管钙化是一个复杂的过程,它不仅取决于钙、磷酸根和pH的物理化学作用,还取决于平滑肌因子,这些因子可能受这些离子以及1,25 - 二羟维生素D3(骨化三醇)和甲状旁腺激素(PTH)的调节。在体外培养9天的大鼠主动脉中膜钙化模型中对这些矿物质和激素进行了检测。钙化通过(45)钙的掺入量进行定量,碱性磷酸酶活性在主动脉匀浆中测量,骨桥蛋白的产生通过培养基的免疫印迹法测量。在1.8 mM钙(1.46 mM游离钙)时,在2.8 mM及以上的磷酸根浓度下会发生钙化。在3.8 mM磷酸根时,在1.10 mM及以上的游离[钙]浓度下会发生钙化。在[钙]×[磷酸根]恒定的情况下,钙化与[钙]成正比,与[磷酸根]成反比。钙化在pH值7.19至7.50之间直接相关,但不受PTH或骨化三醇的影响。钙、磷酸根、骨化三醇和PTH可增加碱性磷酸酶活性和骨桥蛋白的产生。我们得出结论,体外大鼠主动脉钙化需要钙和磷酸根浓度都升高,并且钙而不是磷酸根或两者的乘积是主要决定因素。碱性磷酸酶和骨桥蛋白的诱导表明,钙和磷酸根除了简单的物理化学作用外还有其他作用。尽管PTH和骨化三醇在体内不会增加钙化,但它们对平滑肌有影响,可能会影响体内钙化。血液透析过程中产生的碱度范围内的碱性会增强钙化。

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