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评估锌在皮肤纤维化发生中的作用:一项临床前研究。

Evaluating the role of zinc in the occurrence of fibrosis of the skin: a preclinical study.

作者信息

Pietsch Hubertus, Pering Christiane, Lengsfeld Philipp, Walter Jakob, Steger-Hartmann Thomas, Golfier Sven, Frenzel Thomas, Hütter Joachim, Weinmann Hans-Joachim, Sieber Martin A

机构信息

Contrast Media Research, Bayer Schering Pharma AG, Berlin, Germany.

出版信息

J Magn Reson Imaging. 2009 Aug;30(2):374-83. doi: 10.1002/jmri.21845.

Abstract

PURPOSE

To investigate the possible role of Zn as a trigger for NSF we were using a previously established preclinical model. The depletion of endogenous Zinc ions (Zn) caused by the administration of gadolinium-based contrast agents (GBCAs) has been suggested as a possible pathomechanism for nephrogenic systemic fibrosis (NSF).

MATERIALS AND METHODS

In the Zn supplementation study, rats were injected with Gadodiamide, Omniscan, and Magnevist with or without Zn supplementation. In the Zn depletion study, animals were kept on a Zn-deficient diet or a special control diet and received injections of Omniscan, OptiMARK, Magnevist, Gadovist, and Gd-EDTA. Gd, Zn, and Cu concentrations in tissue were measured and histology of the skin was performed.

RESULTS

As seen in earlier studies, a difference in Gd concentration in the skin was observed following treatment with the different GBCAs. High Gd concentration in the skin correlated with the occurrence of NSF-like skin lesions. We observed no differences in the occurrence of skin lesions between the Zn supplementation and the Zn-deficient groups compared to their respective control groups.

CONCLUSION

We found no significant effect of Zn on the initiation of NSF-like skin lesions. The results further support data from previous studies highlighting the importance of complex stability of the investigated GBCAs.

摘要

目的

为了研究锌作为引发肾源性系统性纤维化(NSF)的触发因素的潜在作用,我们使用了先前建立的临床前模型。钆基造影剂(GBCAs)的给药导致内源性锌离子(Zn)的消耗,这被认为是肾源性系统性纤维化(NSF)的一种可能发病机制。

材料与方法

在锌补充研究中,给大鼠注射钆双胺、欧乃影和马根维显,同时给予或不给予锌补充。在锌消耗研究中,动物被喂食缺锌饮食或特殊对照饮食,并接受欧乃影、优化磁共振、马根维显、钆特酸和钆喷酸葡胺的注射。测量组织中的钆、锌和铜浓度,并对皮肤进行组织学检查。

结果

如早期研究所示,用不同的GBCAs治疗后,皮肤中钆浓度存在差异。皮肤中高钆浓度与NSF样皮肤病变的发生相关。与各自的对照组相比,我们观察到锌补充组和缺锌组之间皮肤病变的发生率没有差异。

结论

我们发现锌对NSF样皮肤病变的起始没有显著影响。结果进一步支持了先前研究的数据,突出了所研究GBCAs的络合物稳定性的重要性。

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