10 Gy 全身照射会增加大鼠模型中冠状动脉粥样硬化、心脏结构和功能退化的风险。
10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model.
机构信息
Division of Cardiothoracic Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
出版信息
Int J Radiat Biol. 2009 Dec;85(12):1089-100. doi: 10.3109/09553000903264473.
PURPOSE
To determine the impact of 10 Gy total body irradiation (TBI) or local thorax irradiation, a dose relevant to a radiological terrorist threat, on lipid and liver profile, coronary microvasculature and ventricular function.
MATERIALS AND METHODS
WAG/RijCmcr rats received 10 Gy TBI followed by bone marrow transplantation, or 10 Gy local thorax irradiation. Age-matched, non-irradiated rats served as controls. The lipid profile and liver enzymes, coronary vessel morphology, nitric oxide synthase (NOS) isoforms, protease activated receptor (PAR)-1 expression and fibrinogen levels were compared. Two-dimensional strain echocardiography assessed global radial and circumferential strain on the heart.
RESULTS
TBI resulted in a sustained increase in total and low density lipoprotein (LDL) cholesterol (190 +/- 8 vs. 58 +/- 6; 82 +/- 8 vs. 13 +/- 3 mg/dl, respectively). The density of small coronary arterioles was decreased by 32%. Histology revealed complete blockage of some vessels while cardiomyocytes remained normal. TBI resulted in cellular peri-arterial fibrosis whereas control hearts had symmetrical penetrating vessels with less collagen and fibroblasts. TBI resulted in a 32 +/- 4% and 28 +/- 3% decrease in endothelial NOS and inducible NOS protein, respectively, and a 21 +/- 4% and 35 +/- 5% increase in fibrinogen and PAR-1 protein respectively, after 120 days. TBI reduced radial strain (19 +/- 8 vs. 46 +/- 7%) and circumferential strain (-8 +/- 3 vs. -15 +/- 3%) compared to controls. Thorax-only irradiation produced no changes over the same time frame.
CONCLUSIONS
TBI with 10 Gy, a dose relevant to radiological terrorist threats, worsened lipid profile, injured coronary microvasculature, altered endothelial physiology and myocardial mechanics. These changes were not manifest with local thorax irradiation. Non-thoracic circulating factors may be promoting radiation-induced injury to the heart.
目的
确定 10 Gy 全身照射（TBI）或局部胸部照射（与放射性恐怖威胁相关的剂量）对脂质和肝功能、冠状动脉微血管和心室功能的影响。
材料和方法
WAG/RijCmcr 大鼠接受 10 Gy TBI 后进行骨髓移植，或接受 10 Gy 局部胸部照射。年龄匹配的非照射大鼠作为对照。比较脂质谱和肝功能酶、冠状动脉血管形态、一氧化氮合酶（NOS）同工型、蛋白酶激活受体（PAR）-1 表达和纤维蛋白原水平。二维应变超声心动图评估心脏的整体径向和环向应变。
结果
TBI 导致总胆固醇和低密度脂蛋白（LDL）胆固醇持续升高（分别为 190 ± 8 对 58 ± 6；82 ± 8 对 13 ± 3 mg/dl）。小冠状动脉的密度减少了 32%。组织学显示，一些血管完全阻塞，而心肌细胞保持正常。TBI 导致细胞周围动脉纤维化，而对照心脏的穿透血管对称，胶原和成纤维细胞较少。TBI 导致内皮型 NOS 和诱导型 NOS 蛋白分别减少 32 ± 4%和 28 ± 3%，纤维蛋白原和 PAR-1 蛋白分别增加 21 ± 4%和 35 ± 5%，120 天后。与对照组相比，TBI 降低了径向应变（19 ± 8 对 46 ± 7%）和环向应变（-8 ± 3 对-15 ± 3%）。同样在 120 天的时间内，仅胸部照射没有发生变化。
结论
10 Gy TBI（与放射性恐怖威胁相关的剂量）加重了脂质谱异常，损伤了冠状动脉微血管，改变了内皮生理和心肌力学。这些变化在局部胸部照射中没有表现出来。非胸部循环因子可能促进了心脏的放射性损伤。
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