Dioscin Regulating Bone Marrow Apoptosis in Aplastic Anemia.
Dioscin Regulating Bone Marrow Apoptosis in Aplastic Anemia.
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薯蓣皂苷调节再生障碍性贫血中的骨髓细胞凋亡。
DOI：
10.2147/dddt.s370506
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发表时间：
2022
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再生障碍性贫血（AA）是一种由CD8+T介导的造血细胞凋亡引起的骨髓衰竭疾病。然而，传统的免疫抑制疗法（IST）具有严重的肝肾毒性，在一些患者中甚至不能达到预期的治疗效果。本研究旨在探讨薯蓣皂苷（DNS）治疗AA的作用及其机制。简单地建立AA小鼠模型并进行评价，采用DNS和阳性对照药物进行干预治疗。干预14 d后，检测大鼠股骨骨髓病理、骨髓单核细胞（BMMCs）凋亡率、骨髓CD34+细胞表面Fas （CD95）表达及Fas信号通路关键蛋白。AA组小鼠模型建立后，与对照组相比，AA组小鼠外周血粒细胞、红细胞、血红蛋白、血小板、网织红细胞数量均显著减少（P < 0.01）。胸骨和股骨的骨髓增生程度极低。不同药物干预后，与组模型相比，DNS组AA小鼠外周血细胞数量明显回升（P < 0.01）。不仅BM-MCs的凋亡率降低（P < 0.01）， CD34+骨髓细胞上CD95分子的表达也显著下降（P < 0.01）， Fas信号通路关键蛋白的表达水平也显著降低（P < 0.01）。DNS可恢复AA小鼠外周血全血细胞减少症和骨髓衰竭。DNS降低Fas信号通路关键蛋白水平，抑制骨髓细胞凋亡，治疗AA。
Aplastic anemia (AA), a disease of bone marrow failure, is caused by CD8+T mediated apoptosis of hematopoietic cells. However, traditional immunosuppressive therapy (IST) has severe liver and kidney toxicity and even cannot achieve the expected therapeutic effect in some patients. Our study is aimed to investigate the effect and mechanism of dioscin (DNS) for treating AA. Briefly, we established and evaluated the AA mouse model, DNS and positive control drugs were used for intervention treatment. After 14 days of intervention, femoral bone marrow pathology, bone marrow mononuclear cells (BMMCs) apoptosis rate, bone marrow CD34+ cell surface Fas (CD95) expression and Fas signaling pathway key proteins were detected. After the establishment of the AA mouse model, the number of peripheral blood cells including granulocytes, erythrocytes, hemoglobin, platelets and reticulocytes in the AA group model was significantly decreased compared with the group control (P < 0.01). The degree of bone marrow hyperplasia in the sternum and femur is extremely low. After different drug interventions, compared with the group model, the number of peripheral blood cells in the AA mice rebounded significantly in group DNS (P < 0.01). Not only that the apoptosis rate of BM-MCs decreased (P < 0.01), meanwhile, the CD95 molecule expressed on the CD34+ bone marrow cells had a significant decline (P < 0.01), and the expression level of the key proteins of Fas signaling pathway was also significantly decreased (P < 0.01). DNS recovered the peripheral pancytopenia and bone marrow failure in AA mice. DNS reduced the key protein of Fas signaling pathway level to inhibit apoptosis of bone marrow cells to treat AA.