Biological effects of high-LET irradiation on the circulatory system

High-linear energy transfer (LET) radiation is generally thought to be more biologically effective in various tissues than low-LET radiation, but whether this also applies to the circulatory system remains unclear. We therefore reviewed biological studies about the effects of high-LET radiation on the circulatory system. We identified 76 relevant papers (24 in vitro, 2 ex vivo, 51 in vivo, one overlapping). In vitro studies used human, bovine, porcine or chick vascular endothelial cells or cardiomyocytes, while ex vivo studies used porcine hearts. In vivo studies used mice, rats, rabbits, dogs or pigs. The types of high-LET radiation used were neutrons, α particles, heavy ions and negative pions. Most studies used a single dose, although some investigated fractionation effects. Twenty-one studies estimated the relative biological effectiveness (RBE) that ranged from 0.1 to 130, depending on radiation quality and endpoint. A meta-analysis of 6 in vitro and 8 in vivo studies (selected based on the feasibility of estimating the RBE and its uncertainty) suggested an RBE of 6.69 (95% confidence intervals (CI): 2.51, 10.88) for in vitro studies and 1.14 (95% CI: 0.91, 1.37) for in vivo studies. The meta-analysis of these 14 studies yielded an RBE of 2.88 (95% CI: 1.52, 4.25). This suggests that high-LET radiation is only slightly more effective than low-LET radiation, although substantial inter-study heterogeneity complicates interpretation. Therapeutic effects have also been reported in disease models. Further research is needed to better understand the effects on the cardiovascular system and to improve radiation protection.

一般认为，高线性能量传递（linear energy transfer, LET）辐射对多种组织的生物学效应强于低LET辐射，但该结论是否同样适用于循环系统仍不明确。为此，本研究针对高线性能量传递辐射对循环系统的影响开展了生物学研究综述。本次综述共纳入76篇相关文献（其中24篇为体外实验、2篇为离体实验、51篇为体内实验，存在1篇重复收录的文献）。体外实验采用了人、牛、猪或鸡的血管内皮细胞或心肌细胞，离体实验则使用了猪心脏组织。体内实验的研究对象包括小鼠、大鼠、兔、犬及猪。本次综述纳入的研究所使用的高线性能量传递辐射类型包括中子、α粒子、重离子及负π介子。多数研究采用单次辐射剂量，仅有部分研究探究了分次照射的生物学效应。共有21项研究估算了相对生物学效应（relative biological effectiveness, RBE），其数值范围为0.1至130，具体取值取决于辐射品质与观测终点。基于估算相对生物学效应及其不确定性的可行性标准，本研究对6项体外实验与8项体内实验开展了荟萃分析，结果显示体外实验的相对生物学效应均值为6.69（95%置信区间（confidence interval, CI）：2.51~10.88），体内实验的相对生物学效应均值为1.14（95% CI：0.91~1.37）。针对上述14项研究的整体荟萃分析结果显示，相对生物学效应均值为2.88（95% CI：1.52~4.25）。该结果表明，高线性能量传递辐射的生物学效应仅略强于低LET辐射，但不同研究间存在显著异质性，这为结果解读带来了挑战。此外，已有研究在疾病模型中报道了高线性能量传递辐射的治疗效应。未来仍需开展更多研究，以进一步阐明高线性能量传递辐射对心血管系统的影响，并优化辐射防护策略。