【摘要】 目的探讨癌性贫血患者 EPO 生成及红系增生的变化,以及 TNF、IFN 等负调控细胞因子对 EPO 生成及红系增生的影响。方法对50例癌性贫血患者、15例癌症无贫血患者及对照组采用放射免疫法检测血清 EPO 水平,ELISA 方法检测血清可溶性转铁蛋白受体(sTIR)、TNF-α、IFN-γ水平,用直线回归方法及相关分析定量分析体内 EPO 生成、红系增生情况及其与 TNF-α、IFN-γ的关系。结果癌性贫血患者血清 EPO 水平为(23.11±10.00)IU/L,明显低于同等程度贫血的缺铁性贫血患者的(43.00±22.00)IU/L(P<0.01);实测值/预估值(O/P)EPO 为0.88(0.54～1.10),明显低于对照组及癌症无贫血患者,后二者之间的 O/P EPO 差异无统计学意义。癌性贫血患者的血清 sTfR 水平(30.8±16.95)nmol/L,高于健康对照组的(17.82±6.76)nmol/L,而低于溶血性贫血患者的(65.75±29.12)nmol/L,差异均有统计学意义(P<0.05);O/P sTIR 为0.89(0.57～1.22),明显低于对照组及癌症无贫血患者,后二者之间 O/P sTfR 差异无统计学意义。正常情况下存在于 log(EPO)与血红蛋白浓度之间以及 log(sTfR)与血红蛋白浓度之间的反比关系消失。癌性贫血患者血清 TNF-α、IFN-γ水平分别为(25.75±26.71)ng/L、(50.49±42.12)ng/L,均显著高于正常对照组及癌症无贫血组。TNF-α、IFN-γ水平与血红蛋白浓度之间呈负相关关系。TNF-α与 O/P EPO、O/P sTfR 之间呈负相关。血清 IFN-γ水平与 O/P EPO 之间无相关关系,与 O/P sTfR 呈负相关。结论 TNF-α、IFN-γ等负调控因子的作用下,内源性 EPO 对贫血的反馈性增生相对不足,以及骨髓红系对 EPO 的反应性增生相对不足参与癌性贫血的发病机制。更多还原

【Abstract】 Objective To explore impaired erythropoiesis and relative inadequacy of erythropoietin production in the anemic cancer patients and the correlation of tumor necrosis factor-α(TNF-α)or inteferon-γ (IFN-γ)with inadequate erythropoietin(EPO)response and impaired erythropoiesis in cancer patients with a- nemia.Methods Fifty adult anemic and 15 non-anemic tumor patients were studied.Serum EPO levels were measured by radioimmunoassay(RIA)and serum soluble transferrin receptor(sTfR).TNF-α and IFN-γ lev- els by enzyme-linked immunosorbent assay(ELISA).Log transformed EPO and sTIR values were used in sta- tistical analysis.The R correlation analyses were performed.Results The mean serum immunoreactive erythropoietin level in anemic cancer patients[(23.11±10.00)IU/L]was not significantly higher than in healthy people(P=0.053),but significantly lower than in IDA patients with similar degree of anemia [(43.00±22.00)IU/L,P<0.01].Both O/P EPO[0.88(0.54～1.10)]and O/P sTfR[0.89(0.57 1.22)]were significantly lower in anemic cancer patients than in controls and in non-anemic cancer patients. There was no significant difference between the latter two groups.Furthermore,the expected inverse linear re- lation between serum EPO and hemoglobin levels was absent in the anemic cancer patients,and so did the re- lation between serum sTfR and hemoglobin levels.There was no correlation between O/P EPO and O/P sTfR. The serum levels of both TNF-α and IFN-γ in anemic cancer patients[(25.75±26.71)ng/L,(50.49± 42.12)ng/L,respectively]were significantly higher than those in healthy controls(both P<0.01)or in nonanemic cancer patients(both 0.01<P<0.05),and so did between non-anemic cancer patients and con- trois.The serum levels of TNF-α were inversely correlated with hemoglobin levels(r=-0.40,P=0.004), O/P EPO(r=-0.32,P=0.025)or O/P sTIR(r=-0.36,P=0.01);while serum levels of IFN-γ were inversely correlated with hemoglobin levels(r=-0.36,P=0.01)or O/P sTfP(r=0.39,P=0.006),but not with O/P EPO.Conclusions Anemia of cancer is due to impaired erythropoiesis and relative inadequacy of EPO production.TNF-α might inhibit EPO production and erythropoiesis,while IFN-γ maybe directly in- hibit erythropoiesis and be independent of EPO response inadequacy.更多还原