论文部分内容阅读
目的研究肿瘤坏死因子-α(TNF-α)、红细胞生成素(EPO)、干扰素-γ(IFN-γ)对肿瘤性贫血(CRA)的作用机制。方法将恶性肿瘤患者分为试验组(肿瘤伴贫血,76例)和对照组(肿瘤无贫血,21例);再将试验组患者照铁代谢参数分为试验Ⅰ组(29例)和试验Ⅱ组(47例),另选择50例健康志愿者作为正常组。用放射免疫法检测各组血清EPO、铁蛋白(SF)水平,以酶联免疫吸附试验检测血清TNF-α、IFN-γ水平。抽取正常骨髓,常规培养,分别加入不同浓度TNF-α、IFN-γ,对骨髓红细胞集落生成单位(CFU-E)计数;培养体系中再加入不同浓度的重组人促红素(rhEPO),对各浓度时CFU-E进行计数。结果试验Ⅰ组、试验Ⅱ组及对照组的血清TNF-α分别为(137.8±13.2),(241.4±19.8),(113.7±12.6)ng·L~(-1);这3组的EPO分别为(513.7±37.1),(268.8±21.9),(94.6±11.4)ng·L~(-1);这3组的IFN-γ分别为(191.5±16.5),(289.7±20.3),(157.9±14.7)ng·L~(-1)。这3组的这3种指标均显著高于正常组的(51.3±8.4),(56.8±7.1),(57.4±7.8)ng·L~(-1),差异有统计学意义(均P<0.05);同时,试验Ⅱ组血清EPO显著高于对照组,但显著低于试验Ⅰ组,差异有统计学意义(P<0.05)。体外细胞培养结果显示,TNF-α、IFN-γ均对正常骨髓CFU-E具有抑制作用,与浓度有依赖性且呈正相关;在培养体系中加入rhEPO,能够改善TNF-α、IFN-γ的抑制作用;在2×10~(-10)~32×10~(-10)mol·mL~(-1)内,rhEPO浓度越高,这种改善作用越明显,但依然无法恢复至正常水平。结论在TNF-α、INF-γ等细胞因子作用下,骨髓红系对EPO的反应性不足,这可能是肿瘤性贫血的发病机制之一。
Objective To investigate the mechanism of action of tumor necrosis factor-α (TNF-α), erythropoietin (EPO) and interferon-γ (IFN-γ) on neoplastic anemia (CRA) Methods The patients with malignant tumor were divided into experimental group (anemia with tumor and 76 cases) and control group (anemia without tumor, 21 cases). The parameters of iron metabolism in experimental group were divided into experimental group Ⅰ (n = 29) and experimental group Ⅱ Group (n = 47). Another 50 healthy volunteers were selected as the normal group. Serum levels of EPO and ferritin (SF) were detected by radioimmunoassay. Serum levels of TNF-α and IFN-γ were detected by enzyme linked immunosorbent assay (ELISA). Normal bone marrow was collected and routinely cultured. Different concentrations of TNF-α and IFN-γ were added to count bone marrow erythrocyte colony forming units (CFU-E). Different concentrations of recombinant human erythropoietin (rhEPO) CFU-E was counted at each concentration. Results The serum levels of TNF-α were (137.8 ± 13.2), (241.4 ± 19.8) and (113.7 ± 12.6) ng · L -1 in group Ⅰ, group Ⅱ and control group, respectively Were (513.7 ± 37.1), (268.8 ± 21.9) and (94.6 ± 11.4) ng · L -1, respectively. The levels of IFN-γ in the three groups were (191.5 ± 16.5), (289.7 ± 20.3) and ± 14.7 ng · L -1. The three indexes in these three groups were significantly higher than those in the normal group (51.3 ± 8.4), (56.8 ± 7.1) and (57.4 ± 7.8) ng · L -1, respectively (all P < 0.05). Meanwhile, the serum EPO of group Ⅱ was significantly higher than that of control group, but significantly lower than that of group Ⅰ (P <0.05). The results of in vitro cell culture showed that both TNF-α and IFN-γ inhibited the expression of CFU-E in normal bone marrow, which was positively correlated with concentration-dependent. In the culture system, rhEPO could improve the expression of TNF-α and IFN- The higher the concentration of rhEPO in the range of 2 × 10 ~ (-10) ~ 32 × 10 ~ (-10) mol · mL ~ (-1), the more obvious the effect was, but it still could not recover to the normal level . Conclusions Under the action of cytokines such as TNF-α and INF-γ, erythroid tissue is not responsive to EPO, which may be one of the pathogenesis of neoplastic anemia.