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目的探讨重组人促红细胞生成素(r HuEPO)治疗多发性骨髓瘤小鼠的疗效及其可能作用机制。方法 420只BALB/c小鼠,荷瘤组410只和正常对照组10只。荷瘤组小鼠均皮下接种1×104个MPC-11骨髓瘤细胞,荷瘤后第5 d随机抽取50只作为荷瘤对照组,余小鼠随机分为3个不同剂量的r HuEPO(10 I U、20 I U、30 I U)治疗组,120只/组。r HuEPO皮下注射,每天1次,连续注射2周后减为1周3次。荷瘤对照组小鼠接受生理盐水皮下注射。荷瘤后动态监测血清M蛋白的出现时间,检测小鼠血红蛋白(Hb)水平,并取皮下结节进行病理检查。测定血清IL-6、TNF-α、TNF-γ、IgG、κ轻链浓度,全血CD4+、CD8+细胞计数(流式细胞分析方法),肿瘤组织的微血管密度(MVD)以及肿瘤细胞凋亡(TUNEL法)。结果荷瘤后22 d检测到荷瘤小鼠血清中出现M蛋白;r HuEPO治疗后,各治疗组的Hb水平及生存时间均高于荷瘤对照组(P<0.05),各治疗组间差异无统计学意义(P>0.05);r HuEPO应用2月后,各治疗组血清IL-6、IgG及κ轻链的浓度均低于荷瘤对照组(P<0.05);荷瘤小鼠的总体生存时间与Hb水平呈正相关(P=0.000)、与血清IL-6水平呈负相关(P=0.009)。结论 r HuEPO明显提高荷瘤小鼠的Hb水平并延长其生存时间,同时降低其血清IL-6水平和M蛋白水平。
Objective To investigate the therapeutic effect and its possible mechanism of recombinant human erythropoietin (r HuEPO) in multiple myeloma mice. Methods 420 BALB / c mice, 410 tumor-bearing groups and 10 normal control group. The tumor-bearing mice were inoculated subcutaneously with 1 × 104 MPC-11 myeloma cells, and 50 mice were randomly selected as tumor-bearing control group on the 5th day after tumor-bearing. The remaining mice were randomly divided into three different doses of r HuEPO (10 IU, 20 IU, 30 IU) treatment group, 120 / group. r HuEPO injected subcutaneously once daily, after two weeks of continuous injection reduced to three times a week. Tumor bearing mice were injected subcutaneously with normal saline. After the onset of tumor, the appearance time of serum M protein was dynamically monitored to detect the level of hemoglobin (Hb) in mice. Subcutaneous nodules were taken for pathological examination. The serum levels of IL-6, TNF-α, TNF-γ, IgG, kappa light chain, whole blood CD4 + and CD8 + cell count (flow cytometry), tumor microvessel density (MVD) and tumor cell apoptosis TUNEL method). Results M protein was found in the serum of tumor-bearing mice on day 22 after tumor-bearing. The levels of Hb and the survival time of each treatment group after r HuEPO treatment were higher than those of tumor-bearing control group (P <0.05) There was no significant difference between the two groups (P> 0.05). After 2 weeks of application of r HuEPO, the concentrations of serum IL-6, IgG and kappa light chain in each treatment group were lower than those in tumor-bearing control group (P <0.05) Overall survival time was positively correlated with Hb level (P = 0.000), and negatively correlated with serum IL-6 level (P = 0.009). Conclusion r HuEPO can obviously increase the Hb level and prolong the survival time of tumor-bearing mice, meanwhile reduce the level of serum IL-6 and M protein.