Angelica sinensis polysaccharide prevents mitochondrial apoptosis by regulating the Treg/Th17 ratio in aplastic anemia (Retracted article. See vol. 22, 2022)
Angelica sinensis polysaccharide prevents mitochondrial apoptosis by regulating the Treg/Th17 ratio in aplastic anemia (Retracted article. See vol. 22, 2022)
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当归多糖通过调节再生障碍性贫血中Treg/Th17比值预防线粒体凋亡
DOI：
10.1186/s12906-020-02995-4
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发表时间：
2020-06-22
影响因子：
3.9
通讯作者：
Cui, Xing
中科院分区：
文献类型：
--
作者：
Chen, Zetao;Cheng, Li;Cui, Xing
当归多糖（Angelica sinensis polysaccharide，ASP）是治疗再生障碍性贫血（再障，再障）的有效药物.本研究旨在探讨ASP是否能通过调节异常水平的调节性T细胞（Treg）/分泌IL-17的CD 4 T细胞（Th 17）比值来纠正再障小鼠线粒体凋亡。照射后4 h内移植DBA/2小鼠淋巴结细胞2 × 106个。各组中的小鼠喂食生理盐水或ASP 2周。体外实验中，于造模第2天分离小鼠骨髓有核细胞（BMNCs）和Treg细胞，加入或不加入ASP进行培养。结果中剂量ASP治疗14 d后，小鼠的白色细胞（WBC）、红细胞（RBC）、血小板（PLT）、BMNC计数和Lin-Sca-1 + c-Kit+（LSK）群体活力与AA组小鼠比较。结果表明，ASP可减轻AA小鼠骨髓细胞线粒体外膜损伤，提高线粒体膜的稳定性，纠正骨髓单个核细胞中ROS和凋亡相关蛋白Bcl-2/Bax比值、caspase-3和caspase-9的异常表达。中剂量ASP也可逆转AA诱导的p-P38/P38和Treg/Th 17比例的变化。在体内观察到ASP对BMNCs Bcl-2/Bax和p-P38/P38比值以及caspase-3和caspase-9表达的影响。结论ASP可能通过抑制AA患者异常的T细胞免疫功能，抑制线粒体凋亡，恢复造血干细胞的功能。
BackgroundAngelica sinensis polysaccharide (ASP) is an effective medicine for aplastic anemia (AA). The present study aims to investigate whether mitochondrial apoptosis in aplastic anemia could be corrected by ASP by adjusting an abnormal level of regulatory T cell (Treg)/ IL-17 secreting CD4 T cell (Th17) ratio.MethodsBALB/c mice were treated with 5.0 Gy Co60 γ -radiation. Then 2 × 106lymph node cells from DBA/2 donor mice were transplanted within 4 h after radiation. The mice in the various groups were fed saline or ASP for 2 weeks. For the in vitro experiment, bone marrow nucleated cells (BMNCs) and Treg cells were sorted from the mice on the 2nd day of modeling, and then cultured with or without ASP.ResultsThe mice treated with the medium dose of ASP for 14 days showed increased white blood cell (WBC), red blood cell (RBC), platelet (PLT), BMNC counts and Lin–Sca-1 + c-Kit+ (LSK) populations viability compared with the mice in the AA group mice. The data showed that ASP decreased damage to the mitochondrial outer membrane, improved the stabilization of the mitochondrial membrane, and corrected the abnormal levels of ROS and mitochondrial-associated apoptosis proteins, including the Bcl-2/Bax ratio and caspase-3 and caspase-9 expression, in BMNCs which were sorted from the bone marrow cells of AA mice. The changes to the p-P38/P38 and Treg/Th17 ratios induced by AA were also reversed by the medium dose of ASP. The same ASP effect including the Bcl-2/Bax and p-P38/P38 ratio, caspase-3 and caspase-9 expression of BMNCs were observed in vivo. The viability of Treg cells were increased by treatment of ASP in vivo.ConclusionsASP might prevent mitochondrial apoptosis to restore the function of hematopoietic stem cells by suppressing abnormal T-cell immunity in AA.