包头医学院学报 ›› 2022, Vol. 38 ›› Issue (12): 1-4.doi: 10.16833/j.cnki.jbmc.2022.12.001

• 基础医学论著 •    下一篇

三氧化二砷对红细胞毒性及能量代谢的影响*

李丽莉, 张泽虹, 马强, 刘治, 李晓晶, 邰玉, 杨忠彬, 段超, 任富玉, 苏燕   

  1. 包头医学院基础医学与法医学院,内蒙古包头 014040
  • 收稿日期:2022-08-03 出版日期:2022-12-25 发布日期:2023-01-06
  • 通讯作者: 苏 燕
  • 基金资助:
    *2021年度自治区留学人员创新创业启动支持计划(新型纳米雄黄的急毒性评价及靶器官病理损伤机制的研究);内蒙古自治区第十批草原英才团队(抗白血病功能性纳米药物研发创新人才团队);花蕾项目(纳米雄黄急毒性评价及药代动力学研究);包头医学院科学研究基金项目(BYJJ-BSJJ 202002)

Effects of Arsenic trioxide on toxicity and energy metabolism of RBCs

LI Lili, ZHANG Zehong, MA Qiang, LIU Zhi, LI Xiaojing, TAI Yu, YANG Zhongbin, DUAN Chao, REN Fuyu, SU Yan   

  1. School of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou 014040, China
  • Received:2022-08-03 Online:2022-12-25 Published:2023-01-06

摘要: 目的: 研究三氧化二砷(arsenic trioxide,As2O3)对红细胞(red blood cells,RBCs)毒性及能量代谢的影响。方法: 用终浓度为0.2 mmol/L、0.4 mmol/L、0.8 mmol/L、1.6 mmol/L、3.2 mmol/L As2O3分别在37 ℃培养箱孵育红细胞48 h,利用酶标仪分别检测红细胞存活率及红细胞溶血率;用终浓度为2.5 mmol/L As2O3孵育红细胞5 h,利用液相色谱串联质谱法进行红细胞内靶向能量代谢产物相对定量分析。结果: 0.2 mmol/L As2O3可提高红细胞存活率(P<0.05),0.4 mmol/L和0.8 mmol/L As2O3对红细胞存活率无明显影响(P>0.05),但高浓度(1.6 mmol/L和3.2 mmol/L)As2O3可降低红细胞的存活率(P<0.05);As2O3致红细胞IC50为5 202 μmol/L;红细胞溶血率随As2O3浓度增高逐渐升高,但低浓度As2O3(0.2 mmol/L和0.4 mmol/L)对溶血率几乎没有影响(P>0.05),0.8 mmol/L组、1.6 mmol/L组和3.2 mmol/L组溶血率增高(P<0.05),但溶血率<6 %,红细胞破坏不严重;能量代谢产物的检测结果表明,2.5 mmol/L As2O3 37 ℃孵育红细胞5 h后,红细胞内的三磷酸腺苷(adenosine triphosphate,ATP)、丙酮酸(pyruvic acid,PA)、还原型烟酰胺腺嘌呤二核苷酸磷酸(reduced nicotinamide adenine dinucleotide phosphate,NADPH)含量均增高(P<0.05)。结论: 低浓度As2O3可能通过促进红细胞糖酵解与磷酸戊糖途径保护红细胞。

关键词: 三氧化二砷, 红细胞, 能量代谢

Abstract: Objective: To study the effects of Arsenic trioxide (As2O3) on the toxicity and energy metabolism of RBCs. Methods: Firstly, RBCs were incubated with As2O3 at the final concentration of 0.2 mmol/L, 0.4 mmol/L, 0.8 mmol/L,1.6 mmol/L and 3.2 mmol/L in 37℃ incubator for 48 h, and then the cell viability and hemolysis rate of RBCs were measured by an enzyme labeling instrument. Finally,RBCs were incubated with As2O3 at a final concentration of 2.5 mmol/L for 5 h, and the relative quantitative analysis of targeted energy metabolites in RBCs was performed by liquid chromatography-tandem mass spectrometry. Results: As2O3 at final concentration of 0.2 mmol/L could improve the cell viability of RBCs, and the difference has statistically significant(P<0.05), 0.4 mmol/L and 0.8 mmol/L As2O3 had no significant effect on the viability of RBCs, but high concentration (1.6 mmol/L and 3.2 mmol/L) As2O3 significantly reduced the viability of RBCs, and the difference has statistically significant(P<0.05). The half maximal inhibitory concentration (IC50) of As2O3 RBCs was 5 202 μmol/L. The hemolysis rate of RBCs increased gradually with the increasing concentration of As2O3, but low As2O3 concentration (0.2 mmol/L and 0.4 mmol/L) had little effect on the hemolysis rate, and the hemolysis rate at 0.8 mmol/L, 1.6 mmol/L and 3.2 mmol/L groups were increased gradually(P<0.05), but the hemolysis rate was less than 6 %, and destruction of seemed not very serious. The results of energy metabolites showed that the contents of adenosine triphosphate (ATP), pyruvate(PA), and nicotinamide adenine dinucleotide phosphate (NADPH) were increased significantly in RBCs after incubated with 2.5 mmol/L As2O3 at 37℃ for 5 h, and the difference had statistically significant (P<0.05). Conclusion: Low concentration of As2O3 may protect RBCs by promoting glycolysis and pentose phosphate pathway.

Key words: Arsenic trioxide, RBCs, Energy metabolism