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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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| 篇名： | 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 |
| TITLE： | Protective mechanism of amifostine on acute radiation injury by regulating gut microbiota |
| 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（150mg/kg），每组10只。照射前30min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4GyX射线一次性全身照射致急性辐射损伤。检测照射前2h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16SrRNA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。 |
| 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 LY201816） gut microbiota. |
| 期刊： | 2024年第35卷第04期 |
| 作者： | 丛悦；李莉；赵艺萌；徐媛媛；拱健婷；关佳莉 |
| AUTHORS： | CONG Yue，LI Li，ZHAO Yimeng，XU Yuanyuan，GONG Jianting，GUAN Jiali |
| 关键字： | 急性辐射损伤；氨磷汀；肠道微生物；16S rRNA序列测序 |
| KEYWORDS： | acute radiation injury； amifostine； gut |
| 阅读数： | 30 次 |
| 本月下载数： | 0 次 |
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