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氨磷汀通过调节肠道菌群对急性辐射损伤的防护作用机制
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          丛 悦 ,李 莉,赵艺萌,徐媛媛,拱健婷,关佳莉(首都医科大学附属北京中医医院北京市中医药研究所,
          北京 100010)


          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2024)04-0459-05
          DOI  10.6039/j.issn.1001-0408.2024.04.14


          摘  要  目的  探究氨磷汀对急性辐射损伤小鼠的防护作用机制。方法  30只C57BL/6J小鼠随机分成正常对照组、模型组和氨磷
          汀组(150 mg/kg),每组10只。照射前30 min氨磷汀组小鼠腹腔注射氨磷汀,正常对照组和模型组小鼠腹腔注射等体积生理盐水,
          然后模型组和氨磷汀组小鼠予4 Gy X射线一次性全身照射致急性辐射损伤。检测照射前2 h和照射后第1、4、7、10、14天小鼠外
          周血中白细胞、血小板和红细胞计数,分析照射后第 7 天各类白细胞(中性粒细胞、淋巴细胞、单核细胞)的比例变化;采用 16S
          rRNA扩增子测序技术分析照射后第7天小鼠粪便中肠道菌群结构,并与各类白细胞进行相关性分析。结果  氨磷汀组小鼠白细
          胞计数在照射后第1、4、7、10天,血小板计数在照射后第10天,红细胞计数在照射后第1天均显著高于模型组(P<0.05)。与正常
          对照组比较,模型组小鼠肠道菌群β多样性发生改变,厚壁菌门相对丰度升高,拟杆菌门相对丰度降低;氨磷汀逆转了上述肠道菌
          群β多样性以及拟杆菌门和厚壁菌门相对丰度的变化。模型组有异芽孢杆菌属、丹毒丝菌纲、丹毒丝菌目和丹毒丝菌科4个差异
          性物种,其丰度与外周血淋巴细胞比例呈显著负相关(P<0.01),氨磷汀组有小鼠乳杆菌和卷曲乳杆菌2个差异性物种,其丰度与
          中性粒细胞比例呈显著负相关(P<0.05)。结论  氨磷汀可通过维持肠道微生物菌群平衡来减轻辐射造成的急性损伤。
          关键词  急性辐射损伤;氨磷汀;肠道微生物;16S rRNA序列测序

          Protective mechanism of amifostine on acute radiation injury by regulating gut microbiota
          CONG Yue,LI Li,ZHAO Yimeng,XU Yuanyuan,GONG Jianting,GUAN Jiali(Beijing  Institute  of  Traditional

          Chinese  Medicine,  Beijing  Hospital  of  Traditional  Chinese  Medicine  Affiliated  to  Capital  Medical  University,
          Beijing 100010, China)

          ABSTRACT   OBJECTIVE  To  explore  the  protective  mechanism  of  amifostine  on  acute  radiation  injury  mice.  METHODS
          Thirty  C57BL/6J  mice  were  randomly  divided  into  normal  control  group,  model  group  and  amifostine  group (150  mg/kg),
          with 10 mice in each group. Thirty minutes before irradiation, the mice in the amifostine group were intraperitoneally injected with
          amifostine;  normal  control  group  and  model  group  were  given  constant  volume  of  normal  saline  intraperitoneally;  then  acute
          radiation  injury  was  induced  by  4  Gy  X-ray  radiation  in  both  model  group  and  amifostine  group.  The  white  blood  cell  count
         (WBC), platelet count and red blood cell (RBC) count in mice were detected 2 hours before irradiation and on days 1, 4, 7, 10
          and  14  after  irradiation;  the  changes  in  the  proportion  of  WBC (neutrophils,  lymphocytes  and  monocytes)  on  the  7th  day  after
          irradiation  were  analyzed.  The  16S  rRNA  high-throughput  sequencing  was  used  to  analyze  the  structure  of  gut  microbiota  in  mice
          feces on the 7th day after irradiation, then its correlation with WBC was analyzed. RESULTS The counts of WBC on the 1st, 4th,
          7th and 10th day after irradiation, platelet count on the 10th day after irradiation and RBC count on the 1st day after irradiation in
          the  amifostine  group  were  significantly  higher  than  those  in  model  group (P<0.05).  Compared  with  normal  control  group,β
          diversity  of  gut  microbiome  showed  significant  change,  relative  abundance  of  Firmicutes  increased  and  that  of  Bacteroidetes
          decreased  in  model  group. Amifostine  could  reverse  the  change  in  β  diversity  of  gut  microbiome,  and  the  relative  abundance  of
          Bacteroidetes  and  Firmicutes.  The  model  group  consisted  of  four  distinct  species,  namely  Allobaculum,  Erysipelotrichia,
          Erysipelotrichales  and  Erysipelotrichaceae,  which  were  significantly  negatively  correlated  with  the  proportion  of  peripheral  blood
          lymphocytes (P<0.01); amifostine group consisted of two distinct species, namely Lactobacillus murinus and L. crispatus, which
          were  significantly  negatively  correlated  with  the  proportion  of  neutrophils (P<0.05).  CONCLUSIONS  Amifostine  significantly
                                                             improves  irradiation-induced  injury  by  regulating  dysbiosis  of
             Δ 基金项目 北京中医医院院级课题暨两院合作课题项目(No.
          LY201816)                                          gut microbiota.
             *第一作者 副研究员,博士。研究方向:放射医学。电话:010-                 KEYWORDS     acute  radiation  injury;  amifostine;  gut
          87906668。E-mail:dove0260@163.com                   microbiota; 16S rRNA gene sequencing


          中国药房  2024年第35卷第4期                                                 China Pharmacy  2024 Vol. 35  No. 4    · 459 ·
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