Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics.

Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics.
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DOI:
10.3390/md20030201
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发表时间:
2022-03-09
期刊:
影响因子:
5.4
通讯作者:
Liu HB
Liu HB
中科院分区:
医学2区
文献类型:
--
作者:
Ma WP;Yin SN;Chen JP;Geng XC;Liu MF;Li HH;Liu M;Liu HB

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造血系统损害是细胞毒药物的严重副作用,促造血药物对降低癌症患者的死亡率非常重要。在前期工作中,我们制备了羊栖菜褐藻糖胶的模拟消化产物DSFF,发现DSFF具有激活巨噬细胞的作用。但是,DSFF是否能促进化疗过程中的造血,还需要更多的研究来进一步评价。在本研究中,DSFF(1.8- 7.2mg/kg,i. p.)对环磷酰胺诱导的小鼠造血损伤的影响及其机制进行了研究。结果表明,DSFF能恢复环磷酰胺所致小鼠外周血白色细胞、中性粒细胞和血小板的数量,并能延缓骨髓细胞减少。基于UPLC/Q-Extraction Orbitrap/MS/MS的脂质组学结果揭示了血清中对小鼠造血损伤有反应的16种潜在脂质生物标志物。其中PC(20:1/14:0)和SM(18:0/22:0)是DSFF发挥保护作用的关键脂质分子。在体外实验中,DSFF(6.25-100 μg/mL)也能促进K562细胞的增殖和分化。目前的研究结果表明,DSFF可以影响体内的血细胞和骨髓细胞,从而显示出良好的潜力和应用价值,在减轻环磷酰胺引起的造血损伤。
Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8–7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25–100 μg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.
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