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

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、还原型谷胱甘肽及组织铁含量。结果OVX组小鼠肠道菌群的物种多样性及丰富度显著增加,引起OVX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。

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.