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用于血管钙化的含氮双膦酸盐:动物实验、系统评价与荟萃分析

Nitrogen-containing bisphosphonate for vascular calcification: animal experiments, systematic review and meta-analysis.

作者信息

Xu Wei, Lu Guoyuan, Gong Lifeng, Tang Weigang, Jiang Wei

机构信息

Department of Nephrology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, 213000, Jiangsu, China.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.

出版信息

BMC Cardiovasc Disord. 2025 Jan 31;25(1):66. doi: 10.1186/s12872-025-04526-w.

DOI:10.1186/s12872-025-04526-w
PMID:39891062
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11783937/
Abstract

BACKGROUND

The purpose of our study was to explore the effect of nitrogen-containing bisphosphonate (N-BP) on vascular calcification (VC) through animal experiments and a meta-analysis.

METHODS

In our animal experiments, Sprague-Dawley (SD) rats were randomly divided into a control group, a VC group, a low-dose zoledronic acid (ZOL) (20 µg/kg) group and a high-dose ZOL (100 µg/kg) group. The calcification of the aortic arch was observed by alizarin red staining. The calcium content of the aortic arch was measured. In our systematic review and meta-analysis, databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database, were searched from their inception to December 20, 2023. Eligible studies comparing N-BP versus no N-BP in the treatment of VC were included.

RESULTS

In our animal experiment, the red-stained calcification structure in the low-dose ZOL group was slightly reduced and the red-stained calcification structure in the high-dose ZOL group was significantly reduced compared with that in the VC. The calcium content in the low-dose ZOL group was slightly lower than that in the VC group, but the difference was not significant (P = 0.08). The calcium content in the high-dose ZOL group was significantly lower than that in the VC group (P < 0.0001). Our meta-analysis of human studies revealed that N-BP did not reduce the arterial calcification score (P = 0.46). Our meta-analysis of animal studies revealed that N-BP did not significantly reduce the arterial calcification score (P = 0.09), but N-BP reduced the arterial calcification area (P < 0.00001), arterial calcium content (P = 0.009) and PO content (P = 0.0001).

CONCLUSIONS

Our animal experiment revealed that high-dose ZOL inhibited VC, but low-dose ZOL did not significantly inhibit VC. Our meta-analysis of human studies revealed that N-BP was not effective in the treatment of VC, but our meta-analysis of animal studies suggested a role of N-BP in inhibiting VC.

摘要

背景

我们研究的目的是通过动物实验和荟萃分析来探讨含氮双膦酸盐(N-BP)对血管钙化(VC)的影响。

方法

在我们的动物实验中,将Sprague-Dawley(SD)大鼠随机分为对照组、VC组、低剂量唑来膦酸(ZOL)(20μg/kg)组和高剂量ZOL(100μg/kg)组。通过茜素红染色观察主动脉弓的钙化情况。测量主动脉弓的钙含量。在我们的系统评价和荟萃分析中,检索了包括PubMed、Embase、Cochrane图书馆、中国知网(CNKI)和万方数据库在内的数据库,检索时间从各数据库建库至2023年12月20日。纳入比较N-BP与未使用N-BP治疗VC的合格研究。

结果

在我们的动物实验中,与VC组相比,低剂量ZOL组红色染色的钙化结构略有减少,高剂量ZOL组红色染色的钙化结构显著减少。低剂量ZOL组的钙含量略低于VC组,但差异不显著(P = 0.08)。高剂量ZOL组的钙含量显著低于VC组(P < 0.0001)。我们对人体研究的荟萃分析显示,N-BP并未降低动脉钙化评分(P = 0.46)。我们对动物研究的荟萃分析显示,N-BP并未显著降低动脉钙化评分(P = 0.09),但N-BP降低了动脉钙化面积(P < 0.00001)、动脉钙含量(P = 0.009)和磷含量(P = 0.0001)。

结论

我们的动物实验表明,高剂量ZOL可抑制VC,但低剂量ZOL并未显著抑制VC。我们对人体研究的荟萃分析显示,N-BP对VC治疗无效,但我们对动物研究的荟萃分析提示N-BP在抑制VC方面有作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/68777d042d3d/12872_2025_4526_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/bb989bdbb5f7/12872_2025_4526_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/bd6ccbcb99cb/12872_2025_4526_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/1da78e8f6e8e/12872_2025_4526_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/68777d042d3d/12872_2025_4526_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/bb989bdbb5f7/12872_2025_4526_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/bd6ccbcb99cb/12872_2025_4526_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/1da78e8f6e8e/12872_2025_4526_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e6/11783937/68777d042d3d/12872_2025_4526_Fig4_HTML.jpg

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