促红细胞生成素抑制急性梗死心肌炎症因子的表达

Erythropoietin suppresses myocardial inflammatory cytokine expression in acute myocardial infarction rats

背景:研究表明,炎症细胞因子可影响心肌梗死后的预后,在心脏重构的进程中起重要作用。同时促红细胞生成素的促红细胞生成之外的非造血效应也被广泛证实:促红细胞生成素可通过与靶细胞膜表面的促红细胞生成素受体结合而减少炎症反应,从而减少心肌缺血后的再灌注损伤。目的:观察重组人促红细胞生成素对大鼠急性心肌梗死后心脏重构中炎症因子表达的影响。方法:通过结扎左冠状动脉前降支建立 SD 大鼠急性心肌梗死模型,分为 5 组,假手术组注射生理盐水,手术对照组造模后注射生理盐水,SB203580 组造模后注射 p38 MAPK 的高选择性阻断剂 SB203580,促红细胞生成素组造模后注射促红细胞生成素注射液,促红细胞生成素+SB203580 组造模后注射促红细胞生成素+SB203580 混合液,分别在造模前、造模后 1 d、1 周、2 周及 4 周进行尾静脉采血,酶联免疫吸附法检测血清中白细胞介素 1β、白细胞介素 6、肿瘤坏死因子α水平变化。结果与结论:造模前各组大鼠血清白细胞介素 1β、白细胞介素 6、肿瘤坏死因子α检测值差异均无显著性意义(P > 0.05)。假手术组各时段白细胞介素 1β、白细胞介素 6、肿瘤坏死因子α检测值差异无显著性意义(P >0.05),其余 4 组不同时段各因子检测值呈现造模后 1 d 最高,造模后 4 周回降的趋势(P < 0.05)。造模后手术对照组血清各因子检测值较其他组升高明显,而假手术组血清各因子检测值均低于其他 4 组(P < 0.05);使用药物进行干预的 3 组中,促红细胞生成素+SB203580 组各因子检测值较低(P < 0.05),而促红细胞生成素组与 SB203580 组各因子检测值差异无显著性意义(P > 0.05)。提示重组人促红细胞生成素抑制了大鼠急性心肌梗死后心脏重构中炎症因子白细胞介素 1β、白细胞介素 6、肿瘤坏死因子α的表达,重组人促红细胞生成素抑制炎症因子表达的机制可能与转化生长因子β1-TAK1-p38 MAPK 信号路径相关。

BACKGROUND： Studies have shown that inflammatory cytokines may ihfluence the prognosis after myocardial infarction, and play an important role in the process of cardiac remodeling. The non-hematopoietic effects of erythropoietin have been confirmed： erythropoietin can reduce the inflammatory reaction through bending with the erythropoietin on the surface of target cell membrane, thus decreasing the reperfusion injury after myocardial ischemia. OBJECTIVE： To observe the effect of recombinant human erythropoietin on the inflammatory factor expression during cardiac remodeling in rats with acute myocardial infarction. METHODS： Sprague Dawley rat models of acute myocardial infarction were established through the ligation ofthe left anterior descending coronary artery. The rats were divided into five groups： sham operation group was injected with normal saline; operation control group was injected with normal saline after modeling; SB203580 group was injected with highly selective p38 MAPK inhibitor SB203580 after modeling; erythropoietin group was injected with erythropoietin after modeling; the erythropoietin＋SB203580 group was injected with erythropoieUn＋SB203580 mixed solution after modeling. The tail vein blood samples were collected before modeling, 1 day, 1 week, 2 weeks and 4 weeks after modeling, and then enzyme-linked immunosorbent assay was used to detect the levels of interleukin-113, interlrukin-6 and tumor necrosis factor-a.RESULTS AND CONCLUSION： There were no significant differences in the levels of interleukin-113, interlrukin-6 and tumor necrosis factor-a between groups before modeling （P 〉 0.05）, There were no significant differences in the levels of interleukin-113, interlrukin-6 and tumor necrosis factor-a between different time points in the sham operation group （P 〉 0.05）, and the levels were highest at 1 day after modeling in the other four groups, and then decreased at 4 weeks after modeling （P 〈 0.05）. After modeling, the level of serum cytokines in the operation control group were higher than those in the other four groups, while level of serum cytokines in the sham operation group was lower than that in the other four groups （P 〈 0.05）; among the three groups intervened with drugs, level of serum cytokines was lower in the erythropoietin＋SB203580 group （P 〈 0.05）, while there was no significant difference in the level of serum cytokines between erythropoietin group and SB203580 group （P 〉 0.05）. Recombinant human erythropoietin can inhibit the expressions of inflammatory factors （interleukin-113, interlrukin-6 and the tumor necrosis factor-a） during cardiac remodeling after rat acute myocardial infarction, and the mechanism of recombinant human erythropoietin for inhibiting the expressions of inflammatory factors may related with the transforming growth factor ~1-TAK1-p38 MAPK signal pathway.