γ-干扰素在小剂量美法仑治愈肿瘤过程中对荷瘤小鼠外周血血小板计数的影响及其意义

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目的:探讨γ-干扰素(IFN-γ)在小剂量美法仑治愈肿瘤过程中对荷瘤小鼠外周血血小板(PLT)计数的影响及其意义。方法:利用单一剂量美法仑治愈荷瘤野生型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、用药后第4、7、11、15、28天内眦静脉取血,肝素抗凝后进行血常规检测,观察两组荷瘤小鼠外周血PLT计数的动态变化并进行比较,了解美法仑治疗后荷瘤小鼠化疗的疗效及其外周血PLT计数的变化与体内IFN-γ免疫功能之间的关系。结果:美法仑用药前两组荷瘤小鼠肿瘤结节的直径和外周血PLT计数比较差异无统计学意义(P>0.05)。7.5 mg/kg美法仑用药后第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,而对照组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美法仑用药后6 h,荷瘤IFN-γ+/-小鼠外周血PLT计数较前明显升高,达(1935±378)×109/L(P<0.01),而荷瘤IFN-γ-/-小鼠外周血PLT计数较前无明显升高,为(1183±186)×109/L(P>0.05),两组数据比较差异具有统计学意义(P<0.01)。美法仑用药1 d以后,荷瘤IFN-γ+/-小鼠外周血PLT计数较前逐渐下降,用药后第11天降至(1158±270)×109/L,恢复至化疗前水平(P>0.05);而荷瘤IFN-γ-/-小鼠外周血PLT计数一直维持在正常水平;两组荷瘤小鼠外周血PLT计数比较差异无统计学意义。结论:小剂量美法仑治疗荷瘤C57BL/6小鼠过程中,IFN-γ免疫功能正常的荷瘤IFN-γ+/-小鼠在用药后6 h出现外周血血小板计数的“一过性”增高,小鼠肿瘤治愈;而IFN-γ免疫功能缺陷的荷瘤IFN-γ-/-小鼠在用药后6 h不出现外周血PLT计数的增加,小鼠肿瘤复发死亡。提示在小剂量美法仑治愈肿瘤过程中荷瘤小鼠外周血PLT计数的升高与其体内IFN-γ的免疫功能密切相关。 Objective: To investigate the effect of interferon-γ (IFN-γ) on the count of peripheral blood platelets (PLT) in tumor-bearing mice during the course of curing low-dose melphalan and its significance. Methods: A single dose of melphalan was used to cure the tumor-bearing wild-type C57BL / 6 mice. Six different IFN-γ +/- and IFN-γ - / - C57BL / 6 mice with the same genetic background and genotypes . The changes of tumor nodule diameter in two groups of tumor-bearing mice after 7.5 mg / kg melphalan treatment were observed. The changes of tumor nodule diameter were observed on the 3rd day before melphalan treatment, 6 hours after treatment, 15,28 days of venous blood, heparin anticoagulant after blood tests to observe the two groups of tumor-bearing mice PLT count dynamic changes and compared to understand the effect of melphalan after chemotherapy in mice with tumor efficacy and The relationship between the change of PLT count in peripheral blood and the immune function of IFN-γ in vivo. Results: There was no significant difference in the diameter of tumor nodules and the PLT count of peripheral blood between the two tumor bearing mice before melphalan treatment (P> 0.05). On the first day after the administration of 7.5 mg / kg melphalan, the tumor nodules in two groups of tumor-bearing mice showed no significant reduction. On the fourth day after the administration, the tumor growth of the tumor-bearing IFN-γ - / - mice was mildly inhibited Progressive increase, and within 2 weeks after treatment, all mice tumor recurrence and death, while the control group IFN-γ +/- mouse tumor nodules progressively shrink, the tumor subsided and cured. At 6 h after the administration of 7.5 mg / kg melphalan, the PLT counts in the tumor-bearing IFN-γ +/- mice were significantly higher than before (1935 ± 378) × 109 / L (P <0.01) (1183 ± 186) × 109 / L (P> 0.05). The difference between the two groups was statistically significant (P <0.01) . After 1 day of melphalan treatment, the PLT counts of tumor-bearing IFN-γ +/- mice decreased gradually compared with those before treatment, and decreased to (1158 ± 270) × 109 / L on the 11th day after treatment, returning to the level before chemotherapy P> 0.05). However, PLT counts in peripheral blood of tumor-bearing IFN-γ - / - mice remained at normal levels. There was no significant difference in PLT count between the two groups of tumor-bearing mice. CONCLUSION: In low-dose melphalan-treated C57BL / 6 mice, the IFN-γ-immunized mice with IFN-γ immunosuppression showed peripheral blood platelet counts at 6 h However, the tumor-bearing IFN-γ - / - mice deficient in IFN-γ did not show an increase in peripheral blood PLT counts within 6 h after drug administration, and the mice died of tumor recurrence. It is suggested that the increase of PLT count in peripheral blood of tumor-bearing mice is closely related to the immune function of IFN-γ in vivo in the course of curing tumor with low-dose melphalan.
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