促红细胞生成素对迟发型脑血管痉挛抑制作用的实验研究

Experimental study of erythropoietin inhibition of delayed cerebral vasospasm after subarachnoid hemorrhage

目的研究全身应用重组人促红细胞生成素(rHuEPO)对蛛网膜下腔出血后(SAH)迟发型脑血管痉挛(DCVS)的抑制作用。方法清洁级雄性wistar大鼠40只随机分为四组:空白组、SAH组、SAH+rHuEPO组、SAH+安慰剂组。采用枕大池2次注血法建立蛛网膜下腔出血模型。注血后7d取血,采用酶联免疫吸附法(ELISA)检测测血浆中内皮素-1(ET-1)含量,原位细胞凋亡检测法(TUNEL)检测颞叶神经元凋亡情况,通过测定基底动脉血管横截面积判断脑血管痉挛情况。结果实验显示SAH后第7dSAH+rHuEPO组基底动脉横截面积比SAH组和SAH+安慰剂组相比明显变大(P<0.01);血浆ET-1浓度SAH+rHuEPO组与SAH组和SAH+安慰剂组相比明显减少(P<0.01);TUNEL染色显示SAH+rHuEPO组皮质神经元凋亡程度较SAH组和SAH+安慰剂组显著减轻。结论早期全身应用rHuEPO可以有效预防SAH后迟发型脑血管痉挛,并有脑保护作用,部分与rHuEPO能抑制ET-1的产生有关。

Objective To study the inhibitory effect of recombinant human erythropoietin （rHnEPO） on delayed cerebral vasospasm （DVCS） after subarachnoid hemorrhage （SAH） in experiment. Methods Forty male rats were equally randomized into four groups： contral, SAH, SAH plus rHuEPO , SAH plus placebo. The rat SAH model was constructed by autologous blood two-injection into the cisterna magna. Seven days after the first blood-injection, the content of endothelin-1 （ET-1） in blood was determined by enzyme-linked immunosorbent assays （ELISA）. TUNEL was used to observe the apoptosis of temporal cortex. The area of each basilar lumen was measured to evaluate the degree of cerebral vasospasm. Results The area of the basilar artery in SAH ＋ rHuEPO group was larger than that in SAH or SAH ＋ placebo group （ P 〈 0. 01 ） ; the concentration of ET-1 in SAH ＋ rHuEPO group was lower than that in SAH or SAH ＋ placebo group （ P 〈 0. O1 ） ; TUNEL revealed that apotosis level of the temporal cortex in SAH ＋ rHuEPO group was lower than that in SAH or SAH ＋ placebo group （ P 〈 0. 01 ）. Conclusion These results suggest that systemic administration of rHuEPO has inhibitory effect on delayed cerebral vasospasm following SAH, and has significant cerebral protective effects. The beneficial effect of rHuEPO may be, in part, related to prevent the augmentation of ET-1.