Zhang H, Holt C M, Malik N, Shepherd L, Morcos S K
Cardiovascular Research Group, Clinical Science Centre, Northern General Hospital NHS Trust, Herries Road, Sheffield S5 7AU, UK.
Br J Radiol. 2000 Oct;73(874):1034-41. doi: 10.1259/bjr.73.874.11271894.
The aim of the study was to determine the effects of radiographic contrast media (RCM) on proliferation and apoptosis of human vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed for either 1 min or 15 min to RCM (diatrizoate, ioxaglate, iopromide, iotrolan) at an iodine concentration of 250 mgl ml-1. Controls were complete growth medium (CGM) and saturated mannitol (osmotic control). [3H]thymidine incorporation was used to determine cell proliferation 24 h after exposure. Apoptosis was determined at 1 h and 6 h by terminal uridine nick end labelling (TUNEL), time lapse video microscopy (TLVM) and DNA electrophoresis. Mean proliferation rates (%) (+/- SEM) (p-values compared with the CGM control) at 1 min and 15 min, respectively, were: diatrizoate: 31.9 (10.6), 5.8 (1.5) (p < 0.001); ioxaglate: 48.4 (10.9), 20.4 (4.5) (p < 0.001); iopromide: 63.4 (8.7), 58.2 (10.2) (p < 0.05); iotrolan: 84.7 (7.3), 72.8 (12.4) (p = ns); saturated mannitol 50.5 (9.6), 45.9 (10.0) (p < 0.001). Mean apoptotic indices (%) (+/- SEM) at 1 h and 6 h following 1 min exposure, respectively, were: CGM: 0.25 (0.13), 0.23 (0.08); diatrizoate: 2.18 (0.19), 2.69 (0.34) (p < 0.001); ioxaglate: 1.90 (0.23), 1.69 (0.02) (p < 0.05); iopromide: 0.59 (0.04), 0.33 (0.02) (p = ns); iotrolan: 0.30 (0.07), 0.27 (0.1) (p = ns); saturated mannitol 2.11 (0.24), 1.4 (0.1) (p < 0.05). After 15 min exposure, apoptosis rates at both 1 h and 6 h, respectively, were: iotrolan: 0.29 (0.17), 0.51 (0.16) (p = ns); diatrizoate: 3.19 (0.81), 11.66 (1.75) (p < 0.001); ioxaglate: 1.88 (0.14), 2.87 (0.20) (p < 0.05); iopromide: 1.06 (0.11), 1.52 (0.15) (p < 0.05); saturated mannitol 1.62 (0.09), 4.63 (0.74) (p < 0.05). TLVM and DNA electrophoresis confirmed the occurence of apoptosis after exposure to RCM. In conclusion, saturated mannitol and all tested RCM, with the exception of iotrolan, (diatrizoate > ioxaglate > iopromide) reduced proliferation and increased apoptosis of HUVECs. The effects were more pronounced with ionic RCM and seem to depend on osmolality as well as the chemical structure of these agents. Endothelial injury and apoptosis may be responsible for some of the side effects associated with intravascular use of RCM.
本研究的目的是确定放射造影剂（RCM）对人血管内皮细胞增殖和凋亡的影响。将人脐静脉内皮细胞（HUVECs）暴露于碘浓度为250mg/ml的RCM（泛影葡胺、碘克沙酸、碘普罗胺、碘曲仑）1分钟或15分钟。对照组为完全生长培养基（CGM）和饱和甘露醇（渗透对照组）。暴露24小时后，采用[3H]胸腺嘧啶核苷掺入法测定细胞增殖。在1小时和6小时时，通过末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）、延时视频显微镜（TLVM）和DNA电泳测定细胞凋亡。1分钟和15分钟时的平均增殖率（%）（±SEM）（与CGM对照组比较的p值）分别为：泛影葡胺：31.9（10.6），5.8（1.5）（p<0.001）；碘克沙酸：48.4（10.9），20.4（4.5）（p<0.001）；碘普罗胺：63.4（8.7），58.2（10.2）（p<0.05）；碘曲仑：84.7（7.3），72.8（12.4）（p=无显著性差异）；饱和甘露醇50.5（9.6），45.9（10.0）（p<0.001）。暴露1分钟后，1小时和6小时时的平均凋亡指数（%）（±SEM）分别为：CGM：0.25（0.13），0.23（0.08）；泛影葡胺：2.18（0.19），2.69（0.34）（p<0.001）；碘克沙酸：1.90（0.23），1.69（0.02）（p<0.05）；碘普罗胺：0.59（0.04），0.33（0.02）（p=无显著性差异）；碘曲仑：0.30（0.07），0.27（0.1）（p=无显著性差异）；饱和甘露醇2.11（0.24），1.4（0.1）（p<0.05）。暴露15分钟后，1小时和6小时时的凋亡率分别为：碘曲仑：0.29（0.17），0.51（0.16）（p=无显著性差异）；泛影葡胺：3.19（0.81），11.66（1.75）（p<0.001）；碘克沙酸：1.88（0.14），2.87（0.20）（p<0.05）；碘普罗胺：1.06（0.11），1.52（0.15）（p<0.05）；饱和甘露醇1.62（0.09），4.63（0.74）（p<0.05）。TLVM和DNA电泳证实暴露于RCM后发生了细胞凋亡。总之，饱和甘露醇和所有测试的RCM（除碘曲仑外）（泛影葡胺>碘克沙酸>碘普罗胺）均降低了HUVECs的增殖并增加了其凋亡。离子型RCM的作用更明显，似乎取决于渗透压以及这些药物的化学结构。内皮损伤和凋亡可能是血管内使用RCM相关一些副作用的原因。
