γ-干扰素在小剂量美法仑治疗肿瘤过程中对荷瘤小鼠外周血红细胞的影响

Significance and function of IFN-γ on the changes of peripheral red blood cell count during tumor-rejection induced by a low dose of melphalan in C57BL/6 mice

关键词:  美法仑  肿瘤  C57BL/6小鼠  γ-干扰素  外周血红细胞

Key words:  melphalan  tumor  C57BL/6 mice  IFN-γ  red blood cells

摘要:

［目的］探讨γ-干扰素（IFN-γ）在小剂量美法仑治疗肿瘤过程中对荷瘤小鼠外周血红细胞的影响。［方法］利用单一剂量美法仑治疗荷瘤野生型C57BL/6小鼠模型，取遗传背景相同、基因型不同的IFN-γ+/- 和IFN-γ-/- C57BL/6小鼠各6只，观察7.5 mg/kg美法仑治疗后两组荷瘤小鼠肿瘤结节直径的变化，并且分别在美法仑用药前第3天、用药后6 h、第4、7、11、15、28 天内眦静脉取血，肝素抗凝后检测外周血RBC数、Hb含量和Hct。 ［结果］美法仑7.5 mg/kg用药后第1天，两组荷瘤小鼠肿瘤结节缩小均不明显；用药后第4天，荷瘤IFN-γ-/- 小鼠肿瘤生长轻度受抑后进行性增大，并在用药后2周内所有小鼠肿瘤复发、死亡；而IFN-γ+/- 小鼠肿瘤的肿瘤结节进行性缩小、肿瘤消退并治愈。7.5 mg/kg美法仑治疗后11 d内，IFN-γ免疫功能不同的荷瘤IFN-γ-/- 和IFN-γ+/- 小鼠外周血RBC计数、Hb含量和Hct之间差异无显著性意义（P>0.05）；美法仑治疗11 d后，IFN-γ免疫功能缺陷的荷瘤IFN-γ-/- 小鼠外周血RBC计数、Hb含量和Hct明显低于IFN-γ免疫功能正常的荷瘤IFN-γ+/- 小鼠，两者比较差异具有显著性意义（P<0.01）。 ［结论］小剂量美法仑治疗后荷瘤小鼠外周血RBC、Hb和Hct的降低与其体内IFN-γ的免疫功能无关，其进行性下降可能与荷瘤小鼠肿瘤复发和肿瘤负荷增大有关。

Abstract:

［Objective］To investigate the significance and function of IFN-γ on the changes of peripheral red blood cells during tumor-rejection induced by a low dose of melphalan in C57BL/6 mice.［Methods］Mouse tumor rejection model induced by a single dose of melphalan was used in this experiment.Different gene-type tumor-bearing mice (immunocompetent mice,IFN-γ+/- and IFN-γ-deficient mice,IFN-γ-/- ),which had the same genetic background of C57BL/6,were treated intraperitoneally with melphalan (7.5 mg/kg).Tumor size was observed and recorded every one to three days subsequently.Blood samples were obtained from orbital venous sinus on different days before and after melphalan treatment,and then complete blood counts were performed.The function of IFN-γ on the efficacy of chemotherapy and the dynamic changes of blood RBC count,HB concentration and Hct in IFN-γ+/- and IFN-γ-/- mice after melphalan treatment were analyzed.［Results］Tumors in IFN-γ-/- mice shrank a little,and then grew gradually in 4 days after melphalan treatment,and tumor relapsed in 14 days after treatment; while tumor volumes decreased progressively and tumor cured at last in IFN-γ+/- mice.There was no significant difference in peripheral blood RBC count,Hb level,Hct between IFN-γ-/- and IFN-γ+/- mice within 11 days after melphalan treatment (P>0.05).The levels of peripheral blood RBC count,Hb and Hct in IFN-γ-/- mice were significant lower than that in IFN-γ+/- mice in days after melphalan treatment (P<0.01).［Conclusions］There was no relationship between the immune function of IFN-γ and the decrease of peripheral blood RBC, Hb and Hct induced by low dose melphalan. The progressive decline in blood RBC count, Hb concentration and Hct after melphalan treatment may be related to tumor recurrence and tumor burden.