粪菌移植缓解放射对小鼠海马神经抑制作用的初步研究  

A preliminary study of fecal microbiota transplantation alleviating inhibition of radiation-induced hippocampal neurogenesis in mice

作　　者：李俊彦 张军军[1] 田野[1] Li Junyan;Zhang Junjun;Tian Ye(Department of Radiotherapy Oncology,the Second Affiliated Hospital of Soochow University,Institute of Radiotherapy Oncology,Soochow University,Suzhou Key Laboratory for Radiation Oncology,Suzhou 215004,China)

机构地区：[1]苏州大学附属第二医院放射治疗科,苏州大学放射肿瘤治疗学研究所,苏州市肿瘤放射治疗学重点实验室,苏州215004

出　　处：《中华放射肿瘤学杂志》2023年第2期152-158,共7页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金(81773223,82102824);江苏省重点研发计划专项(BE2018657);江苏省医学创新团队A类(CXDT-37);苏州市2021年度科技发展计划(医疗卫生科技创新-应用基础研究)(SKJY2021081)。

摘　　要：目的研究全脑照射(WBI)及粪便菌群移植(FMT)对小鼠海马神经发生及肠道菌群组成的影响。方法无特定病原体级雄性ICR小鼠40只(8周龄,30 g)以简单随机抽样法分为对照组(C组)、照射组(R组)、对照+FMT组(C+FMT组)、照射+FMT组(R+FMT组),每组10只。单次剂量10 Gy WBI造模后,C组、R组予磷酸盐缓冲溶液灌胃,C+FMT组、R+FMT组予正常小鼠粪菌悬液灌胃14 d。通过16S rRNA测序、BrdU^(+)/NeuN^(+)免疫荧光染色检测粪便菌群组成、海马神经发生的变化。结果WBI和FMT对小鼠存活率和体重无影响。WBI诱导了海马神经发生抑制及粪便菌群失调,如拟杆菌科、瘤胃菌科分别增加28.6%、102.9%,乳杆菌科下降70.6%(P<0.05)。FMT调节了粪便菌群丰度,如肠杆菌科下降65.1%(P=0.028),而乳杆菌科增加58.2%(P=0.015),并部分缓解了海马神经发生抑制。结论这项初步研究提示FMT缓解了WBI诱导的小鼠海马神经发生抑制及肠道菌群组成紊乱失调。直接作用于小鼠全脑的电离辐射间接扰乱了肠道菌群的结构,而肠道菌群组成的变化也反过来影响了小鼠大脑海马神经发生的程度,肠道菌群与大脑之间存在双向作用。Objective To evaluate the effects of whole brain irradiation(WBI)and fecal microbiota transplantation(FMT)on hippocampal neurogenesis and the composition of gut microbiota in mice.Methods Forty specific pathogen free ICR male mice(8-week-old,weighed 30 g)were divided into four groups by simple random sample method:control group(group C),radiation group(group R),group C+FMT and group R+FMT,10 in each group.Animal models were established by WBI at a dose of 10 Gy by 4 MeV electron beam.In group C+FMT and group R+FMT,mice were gavaged with normal fecal bacteria suspension on day 2 post-irradiation,while those in group C and group R were gavaged with phosphate buffered saline as alternative.Hippocampal tissues and feces in four groups were collected on day 15 post-irradiation.16S rRNA sequencing was used to detect the species and abundance of fecal flora.BrdU^(+)/NeuN^(+)immunofluorescence staining was performed to observe the neurogenesis in hippocampus of mice.Results WBI and FMT had no effect on survival rate and body weight of mice.WBI induced the inhibition of hippocampal neurogenesis and flora disorder.The quantity of Bacteroideae and Rumen bacteria was increased by 28.6%and 102.9%,whereas that of Lactobacillus was significantly decreased by 70.6%(P<0.05).FMT regulated the abundance of bacteria.The abundance of Enterobacteriaceae was significantly declined by 65.1%(P=0.028),while that of Lactobacillus was increased by 58.2%(P=0.015).FMT also promoted hippocampal neurogenesis to some extent after WBI.Conclusions This preliminary study demonstrates that FMT alleviates the inhibition of hippocampal neurogenesis and flora disorder induced by WBI in mice.Ionizing radiation directly acting on the whole brain of mice indirectly disturbs the composition of gut microbiota,which in turn affects the degree of hippocampal neurogenesis in the brain of mice.There is a bidirectional interaction between gut microbiota and brain.

关 键 词：粪便菌群移植 海马神经发生 全脑照射 肠道菌群 

分 类 号：R-332[医药卫生]