中文摘要：

高能α粒子辐射所致基因组DNA损伤形式为复杂的簇集损伤。修复难度大，生物效应严重，目前尚缺乏有效防护药物。前期发现香兰素衍生物VND3207具有抗氧化损伤、促进DNA双链断裂损伤修复的作用．能有效防护低传能线密度（LET）γ射线诱发细胞凋亡和基因组损伤。本研究旨在探讨VND3207对高能α粒子辐射诱发人成纤维细胞基因组DNA损伤的防护效应。细胞克隆形成实验表明，VND3207无论是照射前加药还是照射后加药作用均能增强人成纤维HFS细胞对α粒子的辐射损伤抗性。通过中性单细胞凝胶电泳（彗星电泳）、γ-H2AX免疫荧光簇集点、γ—H2AX蛋白表达水平、细胞微核等多个基因组DNA损伤指标分析，表明了VND3207对α粒子辐射诱发细胞基因组DNA损伤的有效防护作用，其在5～10μmol／L浓度下。就可产生显著辐射防护效果，既能减轻α粒子辐射诱发细胞DNA的原初损伤水平。又能提高细胞的DNA修复能力。因此。VND3207具有维护高能粒子辐照细胞的基因组稳定性的作用。有开发成为抗高LET辐射损伤新药的价值。

英文摘要：

As a high linear energy transfer （LET） radiation, α particles mainly induce DNA clustered damage with low repair efficiency and serious biological effects. There is still no effective radioprotection agent available against the biological detriments induced by particles. The vanillin derivative VND3207 is a novel radioprotection agent with an antioxidant potentiality and protective effects against the genomic DNA damage and apoptosis induced by low LET T-ray. The present study is designed to determine the radioprotective effect of VND3207 against the genomic DNA damage of human fibroblast HFS cells induced by high LET α particles. The clonogenic survival assay shows that VND3207 can significantly enhance radioresistance of HFS cells to the irradiation of α particles, no matter the cells are treated with VND3207 before or after irradiation. Multiple indicators of DNA damage detection, including single cell gel electrophoresis, immnuo-fluorescent γ-H2AX foci, γ-H2AX protein expression and micronuclei assay, demonstrate that VND3207 can effectively decrease the initial DNA double-strand break level as well as increase the cellular DNA repair capacity and reduce the residual damage level. The effective concentration is as low as 10-20 mol/L. In conclusion, VND3207 has radioprotective effects on cell survival and genomic stability against the irradiation of α particles, and it is of value to develop radioprotective drugs against high LET radiation.