三维皮肤组织模型中α粒子诱导旁效应的机制研究-miR-21对氧化代谢的调控

项目名称： 三维皮肤组织模型中α粒子诱导旁效应的机制研究-miR-21对氧化代谢的调控

项目编号： No.31270898

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 杨红英

作者单位： 苏州大学

项目金额： 80万元

中文摘要： 电离辐射诱导旁效应打破了传统的靶理论从而将对低剂量电离辐射健康危害及放疗效率的评估产生重要影响。然而旁效应的机理却仍不清楚。本项目在前期研究发现活性氧（ROS）在旁效应中起着关键作用的基础上，拟在自己构建的三维皮肤组织模型中和二维单层细胞培养条件下研究miRNA对ROS的调控在α粒子诱导旁效应中的作用。以P53结合蛋白1、微核、细胞凋亡和细胞增殖等为指标，观察未受照射旁效应细胞与受照射信号细胞相互作用后的变化；检测信号细胞和旁效应细胞中miR-21和超氧化物歧化酶2（SOD2）表达水平的变化；研究miR-21在旁效应和信号细胞中过表达和被抑制对旁效应的影响，以确证miR-21可调控电离辐射诱导的旁效应；分析miR-21过表达和被抑制对细胞胞内SOD2和ROS水平的影响，论证miR-21可通过调节旁效应细胞和信号细胞的氧化还原状态来实现对旁效应的假说。预期结果将有助于阐明旁效应的分子机制。

中文关键词： 电离辐射诱导的旁效应；TGF-β1；miR-21；活性氧；miR-27a/b

英文摘要： The occurrence of ionizing radiation-induced bystander effects challenges the conventional target dogma. Thus, it may have an impact on estimation of radiation cancer risk, particular at low radiation doses, and outcomes of radiotherapy. However, the underlying mechanisms of bystander response still remain unclear. Based on our previous finding that reactive oxygen species (ROS) play an important role in bystander response, we propose to investigate the effect of regulation of ROS by miR21 in α-particle-induced bystander response in three-dimensional skin model, and compare it to the effect in monolayer cell culture (two-dimensional) as well. Using p53 binding protein 1, micronucleus formation， apoptosis and proliferation as endpoints, observe the alterations in unirradiated bystander cells after co-cultured with irradiated sigaling cell; Measure the change in the expression level of miR21 and superoxide dismutase 2 (SOD2) in signaling and unirradiated bystander cells; Study the effect of overexpressed and inhibited miR21 in signaling and bystander cells on bystander response to confirm that miR21 can modulate radiation-induced bystander effects. Moreover, analyze the effect of overexpressed and inhibited miR21 on cellular SOD2 expression level and ROS level; By adding ROS scavengers and hydrogen peroxide produc

英文关键词： radiation-induced bystander effect；TGF-β1；miR-21；ROS；miR-27a/b