Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
PLoS One. 2013 Jul 22;8(7):e68762. doi: 10.1371/journal.pone.0068762. Print 2013.
Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.
放射性心脏病（RIHD）是胸部、胸壁和乳房肿瘤放疗时，当放射野涵盖心脏全部或部分时产生的一种长期副作用。既往研究表明，己酮可可碱（PTX）联合α-生育酚可减轻局部心脏照射大鼠模型中 RIHD 的表现。但 PTX 和 α-生育酚对这些有益作用的相对贡献尚不清楚。本研究检测了 PTX 单独或与生育三烯酚（一种具有潜在辐射缓解特性的维生素 E 形式）联合应用的效果。采用图像引导照射技术对大鼠心脏进行局部 X 射线照射。照射后 3 个月，大鼠给予载体、PTX 或富含生育三烯酚的制剂联合 PTX 口服治疗。照射后 6 个月，PTX 治疗组的 14 只大鼠中有 5 只出现心律失常。PTX 单独或联合生育三烯酚治疗均未改变心脏放射性纤维化、内皮标志物血管性血友病因子和神经调节蛋白 1 的左心室蛋白表达，或信号转导介质 Akt、Erk1/2 或 PKCα 的磷酸化。另一方面，生育三烯酚减少了心脏肥大细胞和巨噬细胞的数量，但增强了组织因子的表达。虽然这种新的局部心脏照射大鼠模型不支持单独使用 PTX，但生育三烯酚对 RIHD 慢性表现的影响值得进一步研究。
