University Medical Center of the Johannes Gutenberg University Mainz, Institute of Toxicology, Germany.
Br Med Bull. 2011;97:17-26. doi: 10.1093/bmb/ldq044. Epub 2011 Jan 20.
HMG-CoA reductase inhibitors (statins) are widely used in the therapy of hypercholesterolemia. Apart from their lipid-lowering activity, they have pleiotropic effects that are attributed to the inhibition of regulatory proteins, including Ras-homologous (Rho) GTPases. Here, we discuss the potential usefulness of statins to prevent normal tissue damage provoked by radiotherapy. Statins reduce the mRNA expression of pro-inflammatory and pro-fibrotic cytokines stimulated by ionizing radiation in vitro and alleviate IR-induced inflammation and fibrosis in vivo. The currently available data indicate that statins accelerate the rapid repair of DNA double-strand breaks and, moreover, mitigate the DNA damage response induced by IR. Furthermore, statins increase the mRNA expression of DNA repair factors in vivo. Thus, although the molecular mechanisms involved are still ambiguous, preclinical data concordantly show a promising radioprotective capacity of statins.
羟甲基戊二酰辅酶 A 还原酶抑制剂（他汀类药物）广泛用于高胆固醇血症的治疗。除了降低血脂的作用外，它们还具有多效性作用，这归因于对调节蛋白的抑制，包括 Ras 同源（Rho）GTP 酶。在这里，我们讨论了他汀类药物预防放射治疗引起的正常组织损伤的潜在用途。他汀类药物可降低体外电离辐射刺激的促炎和促纤维化细胞因子的 mRNA 表达，并减轻体内 IR 诱导的炎症和纤维化。目前可用的数据表明，他汀类药物可加速 DNA 双链断裂的快速修复，并且减轻由 IR 诱导的 DNA 损伤反应。此外，他汀类药物还可增加体内 DNA 修复因子的 mRNA 表达。因此，尽管涉及的分子机制尚不清楚，但临床前数据一致表明他汀类药物具有有希望的放射防护能力。
