Department of Basic Sciences, Division of Radiation Research, Loma Linda University, Loma Linda, California, United States of America.
PLoS One. 2013 Sep 19;8(9):e75097. doi: 10.1371/journal.pone.0075097. eCollection 2013.
Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer-related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA's Space Shuttle Program, exploration of space will undoubtedly continue.
我们之前的飞行(FLT)小鼠研究结果表明,它们的胸腺和脾脏存在异常,可能会影响免疫防御机制。在这项研究中,亚特兰蒂斯号航天飞机完成为期 13 天的任务返回后,我们进一步评估了 C57BL/6 小鼠的这些器官。我们从 FLT 小鼠和饲养在类似动物围场模块(AEM)中的地面对照小鼠中采集了胸腺和脾脏。我们测定了器官和体重、DNA 片段化以及与 T 细胞和癌症相关的基因表达。尽管胸腺质量没有显著差异,但 FLT 组的 DNA 片段化更大(P<0.01)。FLT 小鼠的脾脏质量单独且相对于体重显著降低(P<0.05)。在 FLT 小鼠的胸腺中,与 AEM 对照组相比,有 6/84 个 T 细胞相关基因受到影响(P<0.05;上调:IL10、Il18bp、Il18r1、Spp1;下调:Ccl7、IL6);有 15/84 个癌症相关基因的表达发生改变(P<0.05;上调:Casp8、FGFR2、Figf、Hgf、IGF1、Itga4、Ncam1、Pdgfa、Pik3r1、Serpinb2、Sykb;下调:Cdc25a、E2F1、Mmp9、Myc)。与 AEM 对照组相比,FLT 小鼠的脾脏中有 8/84 个癌症相关基因受到影响(P<0.05;上调:Cdkn2a;下调:Birc5、Casp8、Ctnnb1、Map2k1、Mdm2、NFkB1、Pdgfa)。我们使用途径分析(细胞凋亡信号和检查点调节)来映射癌症相关基因之间的关系。结果表明,在太空中进行相对较短的飞行任务对这两个器官都有显著影响。研究结果还表明,由于与太空旅行相关的应激源导致的免疫系统异常,在评估癌症和感染等病理学风险以及设计适当的对策时应予以考虑。尽管这是美国宇航局航天飞机计划的最后一次历史性飞行,但对太空的探索无疑将继续。