EPO对大鼠脑缺血-再灌注后炎症损伤的保护作用

摘要

Objective To study on inhibition and mechanism of inflammation of focal cerebral ischemia-reperfusion injury in rats and explore the protective action of EPO to rats with ischemia-reperfusion injury. Methods 216 male SD rats were randomly divided into 3 groups(n = 72) : sham-operated group, ischemia-reperfusion group and EPO treating group. Each group were further divided into 6 subgroups(n = 12) : 3 , 6 ,12 ,24 ,36 ,48 and 72 h after ischemia-reperfusion. Rats were made into the reversible focal cerebral ischemia model by occluding the middle cerebral artery. The Sham-operated group and ischemia-reperfusion group were reper-fused after occluding the middle cerebral artery for 2 hours. The rats of EPO treating group accepted EPO(3 000 U/kg) after occluding the blood flow for 2 hours;While,the equal normal saline were injected to the sham-operated group and ischemia-reperfusion group. Expression of intercellular adhesion moleculesl (ICAM-1) and vascular cell adhesion moleculel (VCAM-1) in hippocampal CA1 were observed by immunohistochemical staining and Western blot at the 6 time points after reperfusion. Results Contrast to the sham-operated group, the expression of ICAM-1 and VCAM-1 in hippocampal CA1 were significantly increased(P<0. 05) ;The expression of ICAM-1 and VCAM-1 were significantly decreased in EPO treating group in comparison to the ischemia-reperfusion group(P<0. 05). Conclusion ICAM-1 and VCAM-1 has a significant role in the inflammation of focal cerebral ischemia-reperfusion injury in rats. EPO could play a neuroprotective action by inhibiting this inflammation.%目的 探讨促红细胞生成素(EPO)对大鼠脑缺血-再灌注的保护作用.方法 将216只雄性大鼠随机分为3组(n=72):假手术组,模型组,EPO干预组;每组再分为缺血-再灌注后3、6、12、24、48和72 h 6个亚组,每亚组大鼠各12只,采用线栓法制备一侧大脑中动脉缺血模型.模型组和EPO干预组缺血2 h后再灌注,EPO干预组于缺血2 h后腹腔注射EPO(3 000 U/kg),假手术组和模型组于同一时间点注射等量生理盐水,然后分别于上述6个时间点断头取材,标本分别用于免疫组化、Western blot分析海马组织细胞间黏附分子-1(ICAM-1)及血管细胞间黏附分子-1(VCAM-1)的表达.结果 与假手术组比较,模型组ICAM-1和VCAM-1蛋白的表达明显增多(P<0.05);与模型组比较,EPO干预组ICAM-1和VCAM-1蛋白的表达明显减少(P<0.05).结论 ICAM-1和VCAM-1蛋白在大鼠脑缺血-再灌注后的炎症反应中起重要作用,EPO对此过程具有抑制作用,从而发挥其神经保护作用.