骨髓间充质干细胞来源外泌体对成年大鼠子宫内膜细胞铁死亡的改善作用及其机制  

Effect and mechanism of exosomes derived from bone marrow mesenchymal stem cells on ferroptosis of endometrial cells in adult rats

作　　者：陈美婷 肖邦 朱怡卿 刘梦 黄金凤 王芳 CHEN Meiting;XIAO Bang;ZHU Yiqing;LIU Meng;HUANG Jinfeng;WANG Fang(Department of Medical Genetics,Naval Military Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学医学遗传学教研室,上海200433

出　　处：《山东医药》2022年第12期35-39,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81971337)

摘　　要：目的观察骨髓间充质干细胞来源外泌体(BMSCs-Exo)对成年大鼠子宫内膜细胞铁死亡的改善作用,并探讨其可能机制。方法取60只成年大鼠,并分为治疗组和损伤组各30例,两组均制备子宫内膜损伤模型,治疗组尾静脉注射BMSCs-Exo(800μg/200 g),损伤组静脉注射等量生理盐水;另取30只成年大鼠作对照(对照组),不制备子宫内膜损伤模型,只静脉注射等量生理盐水。采用透射电子显微镜检测各组子宫内膜细胞线粒体外膜、线粒体脊形态,活体组织二价铁离子测定试剂盒、丙二醛(MDA)检测试剂盒、还原型谷胱甘肽(GSH)含量测定试剂盒、氧化型谷胱甘肽(GSSG)检测试剂盒分别检测各组子宫内膜组织Fe^(2+)、MDA、GSH、GSSG,蛋白印迹法检测各组子宫内膜组织谷胱甘肽过氧化物酶4(GPX4)和4-羟基壬烯酸(4HNE)。结果对照组子宫内膜细胞线粒体双层膜结构完整、线粒体脊清晰可见;损伤组子宫内膜组织中线粒体出现浓缩、膜增厚、脊减小或消失及外膜破裂等细胞铁死亡的特征;治疗组线粒体双层膜结构恢复、线粒体脊增多、线粒体大小正常。与对照组比较,损伤组子宫内膜组织中MDA、Fe^(2+)、GSSG表达升高,GSH表达降低(P均<0.05);与损伤组比较,治疗组MDA、Fe^(2+)、GSSG表达降低,GSH表达升高(P均<0.05)。与对照组比较,损伤组GPX4表达降低,4HNE表达升高(P均<0.05);与损伤组比较,治疗组GPX4表达升高,4HNE表达降低(P均<0.05)。结论BMSCs-Exo对成年大鼠子宫内膜细胞铁死亡有改善作用,其可能机制是通过上调子宫内膜组织中GPX4表达以及下调4HNE表达来实现。Objective To investigate the positive effect of exosomes derived from bone marrow mesenchymal stem cells(BMSCs-Exo)on ferroptosis of endometrial cells in adult rats and to explore its possible mechanism.Methods Sixty adult rats were divided into two groups(injured group and treatment group)with thirty rats in each group.The rats in the treatment group were injected with 800μg/200 g of exo some through tail vein injection,and the injured group with the same amount of normal saline.Another 30 adult rats without endometrial injury and only being injected with the same amount of normal saline were used as controls.Transmission electron microscopy(TEM)was used to detect the changes of mitochondrial outer membrane and mitochondrial ridge of endometrial cells in endometrium mechanical injury models of SD rats before and after BMSCS-Exo treatment.The levels of Fe^(2+),malondialdehyde(MDA),reduced glutathione(GSH)and oxidized glutathione(GSSG)in endometrial tissues of each group were determined by Fe^(2+)assay kit,MDA assay kit,GSH assay kit and GSSG assay kit,respectively.The expression levels of glutathione peroxidase 4(GPX4)and 4-hydroxynonenonic acid(4 HNE)in endometrial tissues of each group were determined by Western blotting.Results In the control group,the mitochondrial bilayer structure of endometrial cells was intact and the mitochondrial ridge was clearly visible.In the injured group,the mitochondria in the endometrial tissue showed the characteristics of ferroptosis,such as concentration,thickening of membrane,reduction or disappearance of ridge and rupture of outer membrane.In the treatment group,the structure of mitochondrial bilayer membrane recovered,the number of mitochondrial ridges increased,and the size of mitochondria was normal.Compared with the control group,the expression levels of MDA,Fe^(2+)and GSSG in the endometrial tissues of the injured group increased,while the expression of GSH decreased(all P<0.05).Compared with the injured group,the expression levels of MDA,Fe^(2+)and GSSG in the treatme

关 键 词：骨髓间充质干细胞 外泌体 子宫内膜损伤 铁死亡 

分 类 号：R711.74[医药卫生—妇产科学]