论文部分内容阅读
目的探讨N-乙酰半胱氨酸(NAC)对化疗所致骨髓抑制的改善作用。方法①体内实验:将C57BL/6j小鼠随机分为正常对照组、环磷酰胺(Cy)所致骨髓抑制模型对照组(ip给予生理盐水)以及模型+NAC 30,90和270 mg·kg-1组,每天1次,连续10 d。给药第4天一次性ip给予Cy 380 mg·kg-1制备骨髓抑制小鼠模型。造模后第1,2,3,4和7天,鼠尾静脉取血20μl检测外周血像,同时取一侧股骨骨髓,检测骨髓单个核细胞(BM-MNC)数目;造模后第1天,检测BM-MNC凋亡和细胞内活性氧(ROS)水平。②体外实验:C57BL/6j小鼠一次性ip给予Cy 380 mg·kg-1后第3天,取BM-MNC进行造血祖细胞培养,在培养体系中加入NAC 0.01,0.1,1和5 mmol·L-1,于第7～12天检测造血祖细胞粒红巨噬巨核系集落形成单位(CFU-Mix)、粒细胞巨噬细胞集落形成单位(CFU-GM)和红系爆式形成单位(BFU-E)数目,观察NAC体外对骨髓抑制模型小鼠造血祖细胞增殖分化的影响。结果①体内实验:与正常对照组相比,ip给予Cy后第1～4天,模型组BM-MNC和外周血白细胞(WBC)数目显著下降,造模后第7天仍未恢复正常。与模型组相比,造模第2天,NAC 270 mg·kg-1组WBC数目降低;其余各时间点,NAC各治疗组的WBC数目无明显差异,NAC 30和90 mg·kg-1组WBC最低值于造模后第4天出现。与模型组比较,造模后第1天NAC 30和90 mg·kg-1组ROS水平降低,BM-MNC凋亡率无明显差异;造模后第1～2天BM-MNC明显增加。②体外实验:与正常对照组相比,模型组造血祖细胞CFU-Mix,CFU-GM和BFU-E数目均明显降低;与模型组比较,NAC 0.1 mmol·L-1能够增加骨髓抑制小鼠骨髓造血祖细胞CFU-GM和BFU-E数目,但NAC 5 mmol·L-1减少模型小鼠CFU-GM,BFU-E和CFU-Mix数目。结论 NAC通过降低ROS水平对化疗所致骨髓抑制有一定的改善作用。
Objective To investigate the effect of NAC on bone marrow suppression induced by chemotherapy. Methods ① In vivo experiments: C57BL / 6j mice were randomly divided into normal control group, cyclophosphamide (Cy) induced bone marrow suppression model control group (ip given saline) and model + NAC 30, 90 and 270 mg · kg- 1 group, 1 day, for 10 days. Myelosuppressive mouse model was prepared by intraperitoneal administration of Cy 380 mg · kg-1 on day 4 after administration. On the 1st, 2nd, 3rd, 4th and 7th days after the model establishment, 20μl of tail vein blood was taken to detect the peripheral blood and the bone marrow of one side was taken to measure the number of bone marrow mononuclear cells (BM-MNC) Day, BM-MNC apoptosis and intracellular reactive oxygen species (ROS) levels were measured. ② In vitro experiments: C57BL / 6j mice were treated with 380 mg · kg-1 of Cy 380 mg once a day, and BM-MNC was used to culture hematopoietic progenitor cells. NAC 0.01, 0.1, 1 and 5 mmol · (CFU-Mix), granulocyte-macrophage colony forming unit (CFU-GM) and erythrocyte burst formation unit BFU-E) were used to observe the effect of NAC on the proliferation and differentiation of hematopoietic progenitor cells in myelosuppression model mice. Results ①In vivo, the numbers of BM-MNC and WBC in the model group decreased significantly from the first day to the fourth day after Cy administration compared with the normal control group, and still remained normal on the 7th day after modeling. Compared with the model group, on the second day after modeling, the number of WBC in 270 mg · kg-1 NAC group decreased. At the other time points, there was no significant difference in the number of WBC in each NAC group. The NAC 30 and 90 mg · kg-1 groups The lowest WBC appeared on the 4th day after modeling. Compared with the model group, the levels of ROS in NAC 30 and 90 mg · kg-1 groups decreased on the first day after model establishment, and there was no significant difference in the apoptotic rate of BM-MNC. The BM-MNC increased significantly on the 1st and 2nd days after model establishment. ② In vitro experiments: compared with the normal control group, the numbers of CFU-Mix, CFU-GM and BFU-E of the model group were significantly decreased; compared with the model group, NAC 0.1 mmol·L -1 increased the number of myelosuppressed mice Bone marrow hematopoietic progenitor cells CFU-GM and BFU-E number, but NAC 5 mmol · L-1 reduced CFU-GM, BFU-E and CFU-Mix number of model mice. Conclusions NAC can improve the myelosuppression induced by chemotherapy by decreasing ROS level.