摘要
背景:再生障碍性贫血的重要发病机制之一是造血干细胞衰竭,如何逆转骨髓衰竭是目前的热点问题。目的:探讨当归多糖对骨髓衰竭小鼠线粒体功能异常的调控作用。方法:将72只ICR小鼠随机分为对照组、模型组和治疗组,每组24只,后两组通过60Coγ射线照射、腹腔注射环磷酰胺和灌胃氯霉素制备再生障碍性贫血模型,然后分别给予生理盐水或200 mg/kg当归多糖喂养2周,对照组不造模,正常喂养。造模后第1,7,14天进行外周血细胞、骨髓单个核细胞计数,并用透射电子显微镜观察骨髓的线粒体超微结构。采用免疫磁珠与流式结合的分选技术从骨髓单个核细胞中分离并纯化Lin-Sca-1+c-Kit+(LSK)细胞,即造血干细胞,检测LSK细胞线粒体膜电位、活性氧水平以及Bcl-2、Bax、cleaved caspase-9、cleaved caspase-3、p38蛋白表达水平。结果与结论:与对照组相比,模型组和治疗组血常规明显异常,骨髓单个核细胞计数明显下降,LSK细胞中线粒体数量减少,线粒体膜电位以及Bcl-2/Bax比值降低,活性氧水平以及cleavedcaspase-9、cleaved caspase-3、p38蛋白表达水平升高(P <0.05)。与模型组相比,治疗组上述异常得到明显改善(P <0.05)。结果提示,当归多糖可能通过上调造血干细胞的线粒体膜电位、增加线粒体膜稳定性,逆转其异常凋亡水平,改善造血功能。
BACKGROUND: Bone marrow failure is an important pathogenesis of aplastic anemia, and how to reverse bone marrow failure is an issue of concern. OBJECTIVE: To investigate the regulatory effect of angelica polysaccharide on the mitochondrial dysfunction in murine aplastic anemia. METHODS: Seventy-two ICR mice were randomly divided into control, model and treatment groups(n=24 per group). The mice in the latter two groups were used to establish the aplastic anemia models by 60 Co γ radiation, intraperitoneal injection of cyclophosphamide and intragastric administration of chloramphenicol, and were then given normal saline or 200 mg/kg angelica polysaccharide for 2 weeks, respectively. The control mice received no intervention. At 1, 7 and 14 days after modeling, peripheral blood cells and bone marrow mononuclear cells were counted, and mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy. After Lin-Sca-1+c-Kit+(LSK) cells were sorted from bone marrow cells, which were hematopoietic stem cells. The mitochondrial membrane potential, levels of reactive oxygen species, and the expression levels of Bcl 2, Bax, cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were detected. RESULTS AND CONCLUSION: Compared with the control group, in the model and treatment groups, there were obvious abnormalities in the peripheral blood routine test was the number of bone marrow mononuclear cells was decreased significantly, the mitochondrial number, mitochondrial membrane potential and Bcl 2/Bax ratio were decreased, and the level of reactive oxygen species and the expression of cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were significantly increased(P < 0.05). After angelica polysaccharide treatment, all above results were significantly improved as compared with the model group(P < 0.05). To conclude, angelica polysaccharide might improve hematopoietic function by up-regulating the mitochondrial membrane potential, increasing the mitochondrial membrane stability and rev
作者
钟萍
崔兴
Zhong Ping;Cui Xing(Department of Rehabilitation Medicine,No.960 Hospital of Chinese PLA,Jinan 250000,Shandong Province,China;Department of Hematology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,Shandong Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2020年第13期2074-2079,共6页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金面上项目(81774080)，项目负责人：崔兴
国家自然科学基金青年基金项目(81202839)，项目负责人：崔兴
泰山学者青年专家人才项目(tsqn201812145)，项目负责人：崔兴~~
关键词
再生障碍性贫血
造血干细胞
LSK细胞
当归多糖
线粒体
细胞凋亡
aplastic anemia
hematopoietic stem cells
LSK cells
angelica polysaccharide
mitochondria
cell apoptosis
