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血管钙化与慢性肾衰竭伴和不伴卵巢切除大鼠皮质骨丢失有关:钙化悖论。

Vascular calcification is associated with cortical bone loss in chronic renal failure rats with and without ovariectomy: the calcification paradox.

机构信息

Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

出版信息

Am J Nephrol. 2011;34(4):356-66. doi: 10.1159/000331056. Epub 2011 Aug 26.

DOI:10.1159/000331056
PMID:21876348
Abstract

BACKGROUND

Increased bone loss has been associated with the development of vascular calcification in patients with chronic renal failure (CRF). In this study, the effect of impaired bone metabolism on aortic calcifications was investigated in uremic rats with or without ovariectomy.

METHODS

CRF was induced by administration of a 0.75% adenine/2.5% protein diet for 4 weeks. In one group, osteoporosis was induced by ovariectomy (CRF-OVX), while the other group underwent a sham-operation instead (CRF). A third group consisted of ovariectomized rats with normal renal function (OVX). At regular time intervals throughout the study, bone status and aortic calcifications were evaluated by in vivo micro-CT. At sacrifice after 6 weeks of CRF, bone histomorphometry was performed and vascular calcification was assessed by bulk calcium analysis and Von Kossa staining.

RESULTS

Renal function was significantly impaired in the CRF-OVX and CRF groups. Trabecular bone loss was seen in all groups. In the CRF-OVX and CRF groups, trabecular bone density was restored after adenine withdrawal, which coincided with cortical bone loss and the development of medial calcifications in the aorta. No significant differences with regard to the degree of aortic calcifications were seen between the two CRF groups. Neither cortical bone loss nor calcifications were seen in the OVX group. Cortical bone loss significantly correlated with the severity of vascular calcification in the CRF-OVX and CRF groups, but no associations with trabecular bone changes were found.

CONCLUSIONS

Cortical rather than trabecular bone loss is associated with the process of calcification in rats with adenine- induced CRF.

摘要

背景

在慢性肾衰竭(CRF)患者中,骨丢失增加与血管钙化的发展有关。在这项研究中,研究了骨代谢受损对尿毒症大鼠主动脉钙化的影响,这些大鼠有无卵巢切除术。

方法

通过给予 0.75%腺嘌呤/2.5%蛋白质饮食 4 周来诱导 CRF。在一组中,通过卵巢切除术(CRF-OVX)诱导骨质疏松症,而另一组则进行假手术(CRF)。第三组由具有正常肾功能的卵巢切除术大鼠组成(OVX)。在整个研究过程中的定期时间间隔,通过体内 micro-CT 评估骨状态和主动脉钙化。在 CRF 后 6 周处死时,进行骨组织形态计量学检查,并通过体钙分析和 Von Kossa 染色评估血管钙化。

结果

CRF-OVX 和 CRF 组的肾功能明显受损。所有组均出现小梁骨丢失。在 CRF-OVX 和 CRF 组中,在用腺嘌呤停药后观察到小梁骨密度恢复,这与皮质骨丢失和主动脉中膜钙化的发展同时发生。在两个 CRF 组之间,主动脉钙化的程度没有明显差异。OVX 组未见皮质骨丢失或钙化。皮质骨丢失与 CRF-OVX 和 CRF 组血管钙化的严重程度显著相关,但与小梁骨变化无关。

结论

在腺嘌呤诱导的 CRF 大鼠中,与钙化过程相关的是皮质骨丢失而不是小梁骨丢失。

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