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哪种碘化造影剂对人椎间盘细胞的细胞毒性最小?

Which iodinated contrast media is the least cytotoxic to human disc cells?

作者信息

Kim Kyung-Hyun, Park Jeong-Yoon, Park Hyo-Suk, Kuh Sung-Uk, Chin Dong-Kyu, Kim Keun-Su, Cho Yong-Eun

机构信息

Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.

Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-gu, Seoul, South Korea.

出版信息

Spine J. 2015 May 1;15(5):1021-7. doi: 10.1016/j.spinee.2015.01.015. Epub 2015 Jan 26.

Abstract

BACKGROUND

Iodinated contrast media (CM) is commonly used for various intradiscal injections such as in discography and endoscopic spinal surgery. However, CM has been shown to be toxic to renal tissue due to its ionic strength and osmolarity and as a result of iodine-induced cytotoxicity, which has raised concern over whether there are similar negative effects on disc cells.

PURPOSE

This in vitro study was designed to identify the least cytotoxic iodinated CM to the human disc cell among four different physiochemical iodinated contrast dyes.

STUDY DESIGN

In vitro laboratory study.

METHODS

Intervertebral disc tissue was obtained by discectomy from a total of 10 lumbar disc patients undergoing surgery and disc cells were isolated. The human disc cells were grown in 3D alginate bead culture with 0, 0.1, 10, and 100 mg/mL CM solutions (ionic dimer, ionic monomer, non-ionic dimer, and non-ionic monomer) and mannitol as a control for 2 days. The living cells were analyzed with trypan blue staining. Fluorescence-activated cell sorting analysis was performed using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining to identify live, apoptotic, and necrotic cells.

RESULTS

Human disc cell death was time- and dose-dependent in response to CM and more necrosis was observed than apoptosis. In addition, non-ionic dimeric CM (iodixanol) showed the least toxic effect on human disc cells, followed by non-ionic monomeric (iopromide), ionic dimeric (ioxaglate), and ionic monomeric CM (ioxithalamate).

CONCLUSIONS

Contrast media is cytotoxic to human disc cells in a dose- and time-dependent manner. This in vitro study revealed that, among four different CM preparations, non-ionic dimeric CM is the least detrimental to human disc cell viability. Careful attention should be paid to the type of CM chosen for discography and endoscopic spinal surgery. It is also necessary to investigate the detrimental effects of CM on disc cells and disc degeneration in further in vivo studies.

摘要

背景

碘化造影剂(CM)常用于各种椎间盘内注射,如椎间盘造影和脊柱内镜手术。然而,由于其离子强度和渗透压以及碘诱导的细胞毒性,CM已被证明对肾组织有毒性,这引发了人们对其是否对椎间盘细胞有类似负面影响的担忧。

目的

本体外研究旨在确定四种不同理化性质的碘化造影染料中对人椎间盘细胞细胞毒性最小的碘化CM。

研究设计

体外实验室研究。

方法

通过椎间盘切除术从总共10例接受手术的腰椎间盘患者中获取椎间盘组织,并分离出椎间盘细胞。人椎间盘细胞在含有0、0.1、10和100mg/mL CM溶液(离子二聚体、离子单体、非离子二聚体和非离子单体)以及甘露醇作为对照的三维海藻酸钠珠培养中培养2天。用台盼蓝染色分析活细胞。使用膜联蛋白V和碘化丙啶(PI)进行荧光激活细胞分选分析以及三维海藻酸钠珠免疫染色,以鉴定活细胞、凋亡细胞和坏死细胞。

结果

人椎间盘细胞死亡对CM呈时间和剂量依赖性,观察到的坏死比凋亡更多。此外,非离子二聚体CM(碘克沙醇)对人椎间盘细胞的毒性作用最小,其次是非离子单体(碘普罗胺)、离子二聚体(碘克酸)和离子单体CM(碘他拉酸)。

结论

造影剂对人椎间盘细胞具有剂量和时间依赖性的细胞毒性。本体外研究表明,在四种不同的CM制剂中,非离子二聚体CM对人椎间盘细胞活力的损害最小。在选择用于椎间盘造影和脊柱内镜手术的CM类型时应格外小心。还需要在进一步的体内研究中调查CM对椎间盘细胞和椎间盘退变的有害影响。

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