中国药理学与毒理学杂志2012，Vol.26Issue(3)：327-332,6.DOI:10.3867/j.issn.1000-3002.2012.03.013
N-乙酰半胱氨酸对化疗所致骨髓抑制的改善作用
Effect of N-acetylcysteine on myelosuppression induced by chemotherapy
摘要
Abstract
OBJECTIVE To explore the effect of N-acetylcysteine ( NAC) on myelosuppression induced by chemotherapy in mice. METHODS In vivo experiments, C57BL/6j mice were randomly divided into normal and myelosuppression groups. Myelosuppression mice were ip given once daily NAC 30, 90 and 270 mg·kg-1 or normal saline, respectively, for 10 consecutive days and were treated (ip) with cyclophosphamide (Cy) on the 4th day to induce myelosuppression. Blood 20 μl from mouse tail was collected to measure peripheral hemogram, and bone marrow in a femur was collected to measure the number of bone marrow mononuclear cells ( BM-MNC) on the 1st, 2nd, 3rd, 4th and 7th days after Cy treatment. Apoptosis and the reactive oxygen species (ROS) level of BM-MNC were measured on the 1st day after Cy treatment. In vitro experiment, the mice were once ip given Cy 380 mg·kg-1 and on the 3rd day the hemotopietic progenitor cells (HPC) were prepared. NAC 0.01, 0.1, 1 and 5 mmol·L-1 were added into the culture system of HPC to measure the number of colony forming unit-granulocyte, erythrocyte, macrophage and megakaryocyte (CFU-Mix), colony forming unit-granulocyte-macrophage (CFU-GM) and burst forming unit-ery-throid (BFU-E). The effect of NAC on proliferation and differentiation of HPC in myelosupressed mice was studied. RESULTS In vivo experiments, the number of BM-MNC and white blood cells (WBC) decreased markedly from the 1st day to the 4th day after Cy treatment and the numbers were still not back to normal on the 7th day after Cy treatment. Compared with normal control, NAC 270 mg'kg~ reduced the number of WBC in peripheral blood on the 2nd day after Cy treatment, and there was no significant difference between the NAC treatment groups at other examination time points, but the time of the lowest WBC count in NAC 30 and 90 mg·kg-1 groups was postponed. Compared with model group, NAC 30 and 90 mg·kg-1 reduced the level of ROS, but increased the count of BM-MNC significantly on the 1 st day and on the 2nd day after Cy treatment. NAC had no marked effects on apoptosis of BM-MNC between NAC treatment groups and model group. In vitro experiment, compared with normal group, the number of CFU-GM, BFU-E and CFU-Mix in myelosuppression model group significantly reduced. Compared with the model group, NAC 0.1 mmol·L-1 increased the numbers of CFU-GM and BFU-E, but NAC 5 mmol·L-1 decreased the number of CFU-GM, BFU-E and CFU-Mix. CONCLUSION NAC improves myelosuppression by reducing ROS level of BM-MNC in myelosuppressed mice.关键词
N-乙酰半胱氨酸/骨髓细胞/药物疗法/造血干细胞Key words
N-acetylcysteine/ bone marrow cells/ drug therapy/ hematopoietic stem cells分类
医药卫生引用本文复制引用
祝晓玲,林志彬..N-乙酰半胱氨酸对化疗所致骨髓抑制的改善作用[J].中国药理学与毒理学杂志,2012,26(3):327-332,6.基金项目
杨森科学委员会中国分会研究基金资助项目(20080276) （20080276）
