促红细胞生成素对局灶性脑缺血再灌注模型大鼠脑组织的保护作用研究  

Protective Effect of Erythropoietin on Cerebral Tissue of Rats with Focal Cerebral Ischemia-reperfusion

作　　者：赵德福[1] 宁显忠[1] 常钦达[1] 杨冬辉[1] 

机构地区：[1]辽宁医学院附属第三医院,辽宁锦州121000

出　　处：《中国药房》2012年第17期1568-1571,共4页China Pharmacy

摘　　要：目的:研究促红细胞生成素(EPO)对局灶性脑缺血再灌注模型大鼠脑组织的保护作用。方法:取大鼠随机分为假手术组、模型组和EPO低、中、高剂量(1 000、3 000、5 000 u.kg-1)组,采用线栓法建立局灶性脑缺血再灌注模型,于缺血2 h时腹腔注射相应药物,分别于缺血再灌注后3、6、12、24、48、72 h断头取海马组织,取材前行神经功能学评分,取材后标本以免疫组化法、蛋白质印迹法分析脑组织中基质金属蛋白酶9(MMP-9)与血管内皮生长因子(VEGF)的表达(n=12)。结果:与假手术组比较,模型组大鼠各时间点神经功能学评分明显升高,再灌注12 h后MMP-9、VEGF表达明显升高(P<0.01);与模型组比较,EPO各剂量组再灌注12 h后神经功能学评分、MMP-9表达明显降低,VEGF表达明显升高(P<0.01);与EPO低剂量组比较,EPO中、高剂量组神经功能评分、MMP-9表达明显降低,VEGF表达明显升高(P<0.05)。结论:EPO能通过抑制MMP-9发挥保护细胞外基质的作用,通过增强VEGF表达以增强组织周围微血管的修复能力,从而减轻局灶性脑缺血再灌注损伤程度而发挥脑保护作用。OBJECTIVE： To study the protective effects of erythropoietin（EPO） on cerebral tissue of rats with focal cerebral ischemia-reperfusion.METHODS： SD rats were randomly divided into sham operation group,model group and EPO low-dose,medium-dose and high-dose（1 000 u·kg-1,3 000 u·kg-1,5 000 u·kg-1） groups.Focal cerebral ischemia-reperfusion model was established by thread occlusion method and given relevant drugs 2 h after ischemia.Before model rats were decollated to collect hippocampus 3,6,12,24,48 and 72 h after ischemia-reperfusion respectively,the neurological scores of the rats were observed.Expressions of MMP-9 and VEGF in cerebral tissue were observed by immunohistochemical staining and Western blot（n=12）.RESULTS： Compared with sham operation group,the neurological scores of model group increased significantly,and the expression of MMP-9 and VEGF of group increased significantly 12 h after reperfusion（P0.01）;compared with model group,the neurological scores and the expression of MMP-9 decreased while the expression of VEGF increased in EPO groups 12 h after reperfusion（P0.01）;compared with EPO low-dose group,the neurological scores and the expression of MMP-9 decreased significantly while the expression of VEGF increased in EPO medium-dose and high-dose groups（P0.05）.CONCLUSION： EPO can protect the extracellular matrix role by decreasing the expression of MMP-9 and enhance the rehabilitation ability of peripheral micrangium by increasing the expression of VEGF to protect cerebral tissue from focal cerebral ischemia-reperfusion injury.

关 键 词：促红细胞生成素 脑缺血再灌注 大鼠 基质金属蛋白酶9 血管内皮生长因子 

分 类 号：R965[医药卫生—药理学]