小剂量美法仑治愈荷瘤小鼠过程中外周血细胞计数的变化及其意义

Changes and significance of peripheral blood count in tumor rejection induced by a low dose of melphalan in C57BL/6 mice

目的:观察在小剂量美法仑治愈荷瘤C57BL/6小鼠过程中外周血细胞计数的变化与肿瘤结节缩小之间的关系,为进一步研究化疗治愈肿瘤的作用机制奠定基础。方法:野生型C57BL/6小鼠皮下接种小鼠淋巴瘤EL4细胞,建立荷EL4肿瘤的小鼠模型。肿瘤接种后12d,12只荷瘤小鼠随机分成2组,7.5mg/kg美法仑单次腹腔内注射,等量生理盐水对照。观察荷瘤小鼠肿瘤结节直径的变化。用药组小鼠分别在7.5mg/kg美法仑治疗前3d、治疗后6h、治疗后第4、7、11、15、28天内眦静脉取血,进行血常规检测,分析荷瘤小鼠外周血象与荷瘤小鼠肿瘤结节缩小之间的相关性。结果:7.5mg/kg美法仑治疗后,荷瘤小鼠肿瘤消退;而对照组荷瘤小鼠肿瘤继续生长。美法仑治疗后6h外周血白细胞为(10.6±2.3)×109/L,与治疗前(9.8±0.32)×109/L比较差异无统计学意义(P>0.05);治疗后第4天外周血白细胞降为(2.9±0.97)×109/L,与治疗前比较差异具统计学意义(P<0.01),随后尽管白细胞数有所回升,但在治疗后第28天仍明显低于化疗前水平(P<0.01)。Hb含量在美法仑治疗后6h由化疗前的(132±7)g/L降为(110±14)g/L(P<0.05),随后Hb含量持续降低,治疗后第7天达最低点(96±5)g/L,以后逐渐升高,治疗后15d恢复至化疗前水平。用药后6h荷瘤小鼠血小板计数升至(1502±142)×109/L,与用药前(914±322)×109/L比较差异具有统计学意义(P<0.01),随后1周内一直维持在高水平,治疗后第11天血小板恢复至化疗前水平。结论:美法仑在使荷瘤小鼠的肿瘤结节缩小的同时可引起外周血白细胞数和血红蛋白浓度的降低,但对血小板无抑制作用。美法仑化疗后1周内血小板计数的增加可能与美法仑的抗肿瘤作用有关。

AIM：To investigate the relationship between changes of peripheral blood counts and tumor rejection induced by a low dose of melphalan in C57BL/6 mice. METHODS：Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice. Twelve days later,7.5 mg/kg melphalan were administered intraperitoneally and the same volume of Normal Saline as control. Tumor sizes were observed and recorded subsequently. Blood samples were obtained from orbital venous sinus on different days before and after melphalan treatment,and then complete blood counts were performed and the relationship between the alterations of blood counts and tumor shrinkage after melphalan treatment was analyzed. RESULTS：Tumor sizes decreased and tumors disappeared after 7.5 mg/kg melphalan treatment; while tumors grow continuously in control mice. The number of WBC was increased a little （10.6±2.3）×10^9/L 6 h after melphalan treatment,but there was no significant difference with mice before melphalan injection （9.8±0.32）×10^9/L （P〉0.05）; The number of WBC decreased significantly at 4^th day after melphalan treatment （P〈0.01）; Later it increased a little,but at 28th day after melphalan it still obviously lower than that of the normal （P〈0.01）. Hemoglobin （Hb） concentration decreased from （132±7） g/L before melphalan treatment to （110±14） g/L at 6 h after melphalan treatment （P〈0.05）. Later,the amount of Hb was decreasing and at 7th day it got to its lowest point （96±5） g/L. It increased gradually back to normal in 2 weeks after melphalan treatment. The platelet count increased to （1502±142）×10^9/L 6 h after melphalan treatment,significantly higher that that （914±322）×10^9/L before melphalan injection （P〈0.01）. It maintained at a high level for one week and it recovered back to normal level at 28^th day after melphalan treatment. CONCLUSION：Tumor shrinkage after melphalan treatment was not related to the decreased number of WBC or RBC,but correlated with the increased number of platelet in 10 days after melphalan treatment.