肠道菌群导致卵巢切除小鼠骨髓内铁死亡的研究
Gut microbiota causes ferroptosis in the bone marrow of ovariectomized mice
谭曾林 1曾菁菁 2刘建纬 3边若瑜 4陈雷1
作者信息
- 1. 温州医科大学附属第一医院骨科,浙江温州 325000
- 2. 温州医科大学宁波院区,浙江宁波 325000
- 3. 温州医科大学基础医学院,浙江温州 325000
- 4. 温州医科大学,浙江温州 325000
- 折叠
摘要
目的 探讨肠道菌群是否激活骨髓内铁死亡引发绝经后骨质疏松症(postmenopausal osteoporosis,PMOP).方法 通过Micro-CT分析正常组及卵巢切除(ovariectomy,OVX)组小鼠的股骨结构;通过16 S rRNA测序分析小鼠的肠道菌群结构;提取小鼠回肠、结肠和股骨的RNA及蛋白,并检测其中炎性因子、紧密连接蛋白及铁死亡相关因子的表达水平;利用试剂盒检测股骨中丙二醛、还原型谷胱甘肱及组织铁含量.结果 0VX组小鼠肠道菌群的物种多样性及丰富度显著增加,引起0VX小鼠肠道屏障功能受损.肠道屏障功能的受损引起骨髓的炎性反应及铁死亡的发生,最终导致了 PMOP的发生发展.结论 肠道菌群能够通过促进OVX小鼠骨髓炎症及骨髓内细胞铁死亡引起PMOP.
Abstract
Objective To explore the mechanism of postmenopausal osteoporosis(PMOP).Methods The femoral structure of normal group and ovariectomized(OVX)mice were analyzed using micro-CT.The gut microbiota structure of mice was analyzed with 16 S rRNA sequencing.RNA and protein were extracted from the ileum,colon and femurs of mice.The expression levels of inflammatory factors,tight junction protein,and ferroptosis related factors were detected.In addition,the content of malondialdehyde(MDA),reduced glutathione(GSH),and tissue iron(Fe)in femurs were detected with the kits.Results The species diversity and richness of gut microbiota in OVX mice significantly increased,which resulted in the impairment of intestinal barrier function in OVX mice.The damage of intestinal barrier function caused bone marrow inflammation and ferroptosis,which eventually contributed to the occurrence and development of PMOP.Conclusion Gut microbiota induced PMOP by promoting bone marrow inflammation and ferroptosis in OVX mice
关键词
肠道菌群/骨质疏松症/炎症/铁死亡Key words
gut microbiota/osteoporosis/inflammation/ferroptosis引用本文复制引用
基金项目
国家自然科学基金(82002279)
浙江省自然科学基金(LGF22H060014)
浙江省科技厅项目(LGF19H070004)
温州市科技局项目(Y2020009)
出版年
2024