Effect of Different Classes of Gadolinium-based Contrast Agents on Control and Nephrogenic Systemic Fibrosis-derived Fibroblast Proliferation
Effect of Different Classes of Gadolinium-based Contrast Agents on Control and Nephrogenic Systemic Fibrosis-derived Fibroblast Proliferation
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DOI：
10.1148/radiol.10091131
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发表时间：
2010-09-01
期刊：
影响因子：
19.7
通讯作者：
Jardine, Alan G.
中科院分区：
文献类型：
--
作者：
Edward, Michael;Quinn, Jean A.;Jardine, Alan G.
目的：研究不同类型的含Gd的造影剂在单层细胞培养中刺激成纤维细胞增殖的能力。材料和方法：国家卫生服务西部格拉斯哥伦理委员会批准了这项研究。将来自健康志愿者(对照组)和肾源性系统性纤维化患者皮损皮肤的成纤维细胞暴露于不同浓度的离子、非离子线性和大环造影剂4d后，测定其对细胞生长的影响。选择对成纤维细胞生长刺激作用最大的最低浓度造影剂，测定8d后对成纤维细胞生长的影响。用酶联免疫吸附试验检测造影剂对透明质酸和胶原合成的影响。结果：线性Gd造影剂(加多二胺、加多福塞胺、加多喷酸地葡胺、加多贝酸二葡胺)对成纤维细胞增殖的刺激作用在0.1mmo1/L时最大，细胞数增加2.3倍。大环造影剂(加得特里酸和加多特利多)在浓度为5 mmol/L时对成纤维细胞的增殖刺激作用最强，参比剂(N-甲基葡萄糖胺、Gd、乙二胺四乙酸和三氯化Gd)在浓度为0.01 mm o l/L时刺激成纤维细胞增殖，在大于1 m ol/L时对成纤维细胞有毒性作用，生长曲线支持量效关系。Gadoverset胺、Gadobenate Diglumine、Gadodiamide、Gadadentetate Diglumine(0.1 mmol/L)和Gadentetate Diglumine(0.01 mmol/L)均能促进透明质酸合成，而对胶原合成无明显影响。结论：本研究为不同浓度的Gd络合物促进人成纤维细胞增殖提供了证据。
Purpose: To determine the ability of different types of gadolinium-based contrast agents (GBCAs) to stimulate fibroblast proliferation in monolayer cell culture.Materials and Methods: The National Health Service West Glasgow Ethics Committee granted approval for this study. Fibroblasts established from healthy volunteers (control subjects) and from lesional skin of patients with nephrogenic systemic fibrosis were exposed to a range of concentrations of ionic and nonionic linear and macrocyclic contrast agents over 4 days, and the effect on growth was determined. The lowest concentration of contrast agent that stimulated the maximum effect on fibroblast growth was selected for determination of its effect on fibroblast growth over 8 days. The effect of contrast agents on hyaluronan and collagen synthesis was determined with an enzyme-linked immunosorbent assay. Responses were assessed with analysis of variance (general linear model).Results: The linear gadolinium contrast agents (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine) produced a maximum stimulation of fibroblast proliferation at a concentration of 0.1 mmol/L, with cell numbers increasing up to 2.3-fold. The macrocyclic contrast agents (gadoteric acid and gadoteridol) produced a maximum stimulation of fibroblast proliferation at a concentration of 5 mmol/L. The reference gadolinium agents (N-methylglucamine gadolinium ethylenediaminetetraacetic acid and gadolinium trichloride) stimulated fibroblast proliferation at a concentration of 0.01 mmol/L and were toxic at a concentration greater than 1 mmol/L. Growth curves supported the dose-response observations. Hyaluronan synthesis was stimulated by gadoversetamide, gadobenate dimeglumine, gadodiamide, and gadopentetate dimeglumine at a concentration of 0.1 mmol/L and by gadolinium trichloride at a concentration of 0.01 mmol/L, whereas collagen synthesis was unaffected.Conclusion: This study provides evidence that different classes of gadolinium chelates stimulate human fibroblast proliferation.