当归多糖干预再生障碍性贫血模型小鼠线粒体功能异常机制研究

目的:研究当归多糖(ASP)对再生障碍性贫血(AA)模型小鼠线粒体功能异常的作用机制。方法:AA小鼠随机分为对照组、再障组和治疗组,再障组与治疗组通过60Coγ、腹腔注射环磷酰胺和氯霉素造模后,分别用生理盐水或ASP喂养2周。透射电子显微镜观察骨髓的线粒体超微结构。从骨髓细胞中分离出Lin-Sca-1+c-Kit+(LSK)细胞,通过流式细胞仪检测线粒体膜电位(MMP),并进行活性氧(ROS)、丙二醛(MDA)、细胞色素氧化酶(COX)和单胺氧化酶(MAO)的相关检测。结果:与对照组比较,再障组和治疗组骨髓的单个核细胞、BFU-Es和CFU-Es、LSK细胞中的线粒体数量减少,MMP降低。应用ASP干预后,骨髓的单个核细胞、BFU-Es和CFU-Es等数值相比再障组显著增加。ASP可以纠正LSK线粒体数量下降的趋势,ASP纠正AA模型小鼠异常的MAO和COX水平,并通过降低ROS和MDA,纠正异常的膜电位而改善线粒体的功能(P<0.05或P<0.01)。结论:ASP可能通过上调线粒体膜电位、改善线粒体膜稳定性,纠正AA干细胞的过度凋亡。

Mechanism of Angelica Sinensis Polysaccharide Intervention on Mitochondrial Function Abnormality in Aplastic Anemia Model Mice

Objective:To study the mechanism of angelica sinensis polysaccharide(ASP) on mitochondrial dysfunction in aplastic anemia( AA) model mice.Methods:AA mice were randomly divided into control group,aplastic anemia group and treatment group. The aplastic anemia group and the treatment group were treated with ~(60)Coγ,intraperitoneal injection of cyclophosphamide and chloramphenicol,and were treated with normal saline or ASP for 2 weeks respectively. The mitochondrial ultrastructure of bone marrow was observed by transmission electron microscopy. Lin~-Sca-1~+c-Kit~+(LSK) cells were isolated from bone marrow cells,and mitochondrial membrane potential(MMP) was detected by flow cytometry,and reactive oxygen species(ROS),malondialdehyde(MDA),and cytochrome oxidase(COX) and monoamine oxidase(MAO) were examined. Results:Compared with the control group,the number of mitochondria in the mononuclear cells,BFU-Es and CFU-Es,LSK cells in the bone marrow of the aplastic anemia group and the treatment group decreased,and the MMP decreased. After the intervention of ASP,the numbers of mononuclear cells,BFU-Es and CFU-Es in bone marrow were significantly increased compared with the aplastic anemia group. ASP can correct the decline in the number of mitochondria in LSK. ASP corrected the abnormal MAO and COX levels in AA model mice and improved mitochondrial function by reducing ROS and MDA and correcting abnormal membrane potential(P< 0.05 or P< 0.01). Conclusion:ASP may correct the excessive apoptosis of AA stem cells by up-regulating mitochondrial membrane potential and improving mitochondrial membrane stability.