Ghosh S N, Wu Q, Mäder M, Fish B L, Moulder J E, Jacobs E R, Medhora M, Molthen R C
Department of Medicine, Division of Pulmonary and Critical Care, Medical College of Wisconsin, Milwaukee, WI, USA.
Int J Radiat Oncol Biol Phys. 2009 May 1;74(1):192-9. doi: 10.1016/j.ijrobp.2009.01.006.
To study vascular injury after whole thoracic irradiation with single sublethal doses of X-rays in the rat and to develop markers that might predict the severity of injury.
Rats that received 5- or 10-Gy thorax-only irradiation and age-matched controls were studied at 3 days, 2 weeks, and 1, 2, 5, and 12 months. Several pulmonary vascular parameters were evaluated, including hemodynamics, vessel density, total lung angiotensin-converting enzyme activity, and right ventricular hypertrophy.
By 1 month, the rats in the 10-Gy group had pulmonary vascular dropout, right ventricular hypertrophy, increased pulmonary vascular resistance, increased dry lung weights, and decreases in total lung angiotensin-converting enzyme activity, as well as pulmonary artery distensibility. In contrast, irradiation with 5 Gy resulted in only a modest increase in right ventricular weight and a reduction in lung angiotensin-converting enzyme activity.
In a previous investigation using the same model, we observed that recovery from radiation-induced attenuation of pulmonary vascular reactivity occurred. In the present study, we report that deterioration results in several vascular parameters for </=1 year after 10 Gy, suggesting sustained remodeling of the pulmonary vasculature. Our data support clinically relevant injuries that appear in a time- and dose-related manner after exposure to relatively low radiation doses.
研究大鼠单次亚致死剂量胸部X线照射后的血管损伤,并开发可预测损伤严重程度的标志物。
对接受5 Gy或10 Gy仅胸部照射的大鼠以及年龄匹配的对照组在3天、2周、1个月、2个月、5个月和12个月时进行研究。评估了几个肺血管参数,包括血流动力学、血管密度、全肺血管紧张素转换酶活性和右心室肥大。
到1个月时,10 Gy组的大鼠出现肺血管缺失、右心室肥大、肺血管阻力增加、肺干重增加、全肺血管紧张素转换酶活性降低以及肺动脉扩张性降低。相比之下,5 Gy照射仅导致右心室重量适度增加和肺血管紧张素转换酶活性降低。
在先前使用相同模型的研究中,我们观察到辐射诱导的肺血管反应性减弱可恢复。在本研究中,我们报告10 Gy照射后1年内多个血管参数出现恶化,提示肺血管持续重塑。我们的数据支持在暴露于相对低辐射剂量后以时间和剂量相关方式出现的临床相关损伤。