在大剂量5-氟尿嘧啶治愈荷瘤小鼠过程中外周血细胞的变化与肿瘤消退之间的相关性分析  

Relationships between tumor shrinkage and peripheral blood cell changes during tumor-rejection induced by a high dose of 5-FU in C57BL/6 mice

作　　者：李传刚[1] 李墨林[2] 舒晓宏[3] 刘用楫[1] Michael Notter 秦志海 

机构地区：[1]大连医科大学附属二院外科,辽宁大连116027 [2]大连医科大学基础医学院病理生理学教研室,辽宁大连116027 [3]大连医科大学药学院,辽宁大连116027 [4]德国洪堡大学CBF血液肿瘤科,德国柏林12200 [5]德国洪堡大学CBF肿瘤免疫研究所,德国柏林12200

出　　处：《细胞与分子免疫学杂志》2008年第2期156-158,共3页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家留学基金资助及辽宁省自然科学基金资助项目(20062156)

摘　　要：目的:观察在单一剂量5-氟尿嘧啶(5-FU)治愈荷瘤小鼠过程中外周血细胞数量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:利用单一剂量5-FU治愈荷瘤野生型C57BL/6小鼠模型,荷瘤小鼠腹腔内分别注入25、75、135mg/kg的5-FU,等量生理盐水对照,确定5-FU治愈肿瘤的量效关系。然后,再取6只荷瘤小鼠,分别在75mg/kg5-FU治疗前3d、治疗后第1、4、7、11、15、28天内眦静脉取血,进行血常规检测,分析外周血白细胞、血红蛋白和血小板的变化与荷瘤小鼠肿瘤结节缩小之间的相关性。结果:75、135mg/kg的5-FU均可使荷瘤小鼠的肿瘤结节在治疗后1周内逐渐缩小、直至消退,因此5-FU治愈荷瘤小鼠的最低有效量为75mg/kg。75mg/kg5-FU治疗后第1天外周血白细胞降为(5.0±1.1)×109/L,并持续到化疗后第4天,与治疗前(9.5±1.58)×109/L比较差异有统计学意义(P<0.01);5-FU治疗后第7～15天外周血白细胞的数量升至化疗前水平,随后逐渐下降,在治疗后第28天降至(5.9±1.96)×109/L,低于化疗前水平(P<0.01)。Hb含量在5-FU治疗后第1天也出现降低,由化疗前的(133±7)g/L降为(112±9)g/L,差异有统计学意义(P<0.01),随后Hb含量持续在低水平,治疗后15d逐渐恢复至化疗前水平。75mg/kg的5-FU对荷瘤小鼠血小板的抑制作用不明显,反而在治疗后第1、11天出现2次血小板一过性增高(P<0.01)。结论:75mg/kg5-FU可引起外周血白细胞数和血红蛋白浓度的降低,但对血小板的抑制作用不明显。5-FU发挥抗肿瘤作用使荷瘤小鼠的肿瘤结节缩小与化疗后外周血白细胞和Hb的降低无关,而与化疗后第1天血小板计数的增加有关。AIM： To investigate the relationship between the alterations of complete blood counts and tumor shrinkage during tumor rejection induced by a high dose of 5-FU in C57BL/6 mice. METHODS： Wild type C57BL/6 tumor-bearing mice were treated with different doses of 5- FU intraperitoneaUy. 75 mg/kg 5-FU was the minimal effective dose of 5-FU that could cure the tumor-bearing mice. Then another 6 tumor-bearing mice were treated intraperitoneally with 5-FU （75 mg/kg）. Blood samples were obtained from orbital venous sinus on different days before and after 5-FU treatment, and then complete blood counts were performed and the relationship between the alterations of blood counts and tumor shrinkage after 5-FU treatment was analyzed. RESULTS： Tumor sizes decreased steadily and tumors disappeared within the first week after 5-FU treatment; and at the same time 75 mg/kg 5-FU also had side effects on peripherial blood cells. The number of WBC significantly decreased from the first day after 5-FU treatment （P〈0.001）. But during the 7 th to 15 th day the number of WBC rebounced back to normal level （ P 〉 0.05 ）. Later it decreased again and it couldn＇t recover back to normal level at the 28th day after 5-FU treatment （ P 〈 0.01 ）. The concentration of Hb decreased at the first day and lasted for 2 weeks （P〈 0.01 ）. It increased gradually back to normal in 2 weeks after 5-FU treatment. The inhibitory effect of 5-FU on platelets count was not obvious. The platelet count increased significantly at the first and at the 11th day after 5-FU treatment respectively （P〈0.01）. CONCLUSION： Tumor shdnkage after 5-FU treatment is not related to the decreased number of WBC or RBC, but correlated with the increased number of platelet at the first day after 5-FU treatment.

关 键 词：5-氟尿嘧啶(5-FU) 肿瘤治愈 淋巴瘤 C57BL/6小鼠 血小板计数 

分 类 号：R730.5[医药卫生—肿瘤]