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钆塞酸二钠暴露后肝肾损伤大鼠的组织钆沉积:电感耦合等离子体质谱法(ICP-MS)评估

Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

作者信息

Sato Tomohiro, Tamada Tsutomu, Watanabe Shigeru, Nishimura Hirotake, Kanki Akihiko, Noda Yasufumi, Higaki Atsushi, Yamamoto Akira, Ito Katsuyoshi

机构信息

Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan,

出版信息

Radiol Med. 2015 Jun;120(6):557-62. doi: 10.1007/s11547-014-0492-y. Epub 2015 Jan 9.

Abstract

PURPOSE

This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis.

MATERIALS AND METHODS

Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats.

RESULTS

ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group.

CONCLUSIONS

Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

摘要

目的

本研究旨在通过电感耦合等离子体质谱法(ICP-MS)对暴露于钆塞酸二钠(Gd-EOB-DTPA)的肝肾损伤大鼠的组织钆(Gd)沉积进行定量,并比较主要器官中Gd分布的差异,以探究其作为肾源性系统性纤维化可能触发因素的作用。

材料与方法

对五只肝肾损伤大鼠(5/6肾切除,伴有四氯化碳诱导的肝纤维化)注射Gd-EOB-DTPA。进行组织学评估,并在最后一次注射后7天通过电感耦合等离子体质谱法(ICP-MS)测量皮肤、肝脏、肾脏、肺、心脏、脾脏、膈肌和股四头肌的Gd含量。此外,对五只肾损伤大鼠注射Gd-EOB-DTPA,并将组织Gd沉积程度与肝肾损伤大鼠进行比较。

结果

ICP-MS分析显示,肝肾损伤组(分别为42.6±20.1、17.2±6.1、8.4±3.2μg/g)肾脏、脾脏和肝脏中的Gd沉积显著高于肾损伤组(分别为17.2±7.7、5.4±2.1、2.8±0.7μg/g)(p=0.009-0.047);其他器官未发现显著差异。在肝肾损伤组中,Gd主要沉积在肾脏,其次是脾脏、肝脏、肺、皮肤、心脏、膈肌和股四头肌。组织病理学研究显示肝肾损伤组存在肝纤维化。

结论

与肾损伤大鼠相比,暴露于Gd-EOB-DTPA的肝肾损伤大鼠肾脏、脾脏和肝脏中的组织Gd沉积显著增加,这可能是由于泌尿和胆道系统双重排泄途径受损所致。

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