目的 对7日龄缺氧缺血性脑损伤(hypoxic ischemic brain damage,HIBD)大鼠进行促红细胞生成素干预,并对血管内皮生长因子(vascular endothelial growth factor,VEGF)及核因子-κB(nuclear factor kappa B,NF-κB)表达的变化情况进行检测分析。方法 将75只SD新生大鼠按照随机数字表分为三组:1)假手术组 取颈部正中切口,接着游离左侧颈总动脉,并进行切口缝合;2)HIBD组 分离左侧颈总动脉,接着游离血管并行结扎,缝合后放入含氧量为 8% 的环境中2 h;3)EPO处理组 游离并结扎左侧颈总动脉,随后放于含氧量为8%的环境中2 h,并腹腔内注射 rhEPO 1次 (剂量:5 000 U/kg)。于6、12、24、72 h后分别留取脑标本,并对脑组织中VEGF及NF-κB的表达情况进行检测。结果 1)与假手术组对比,HIBD组和EPO处理组中VEGF的表达有明显增高(P＜0.05);2)HIBD组NF-κB表达高于假手术组(P＜0.05), HIBD组高于EPO处理组(P＜0.05)。结论 促红细胞生成素有增高VEGF蛋白表达、降低NF-κB蛋白表达作用,这一机制可能对新生大鼠缺氧缺血性脑损伤起保护作用的机制之一。
Abstract
Objective To investigate the effects of erythropoietin on vascular endothelial growth factor(VEGF) and nuclear factor kappa B (NF-κB )expression in neonatal rats with hypoxic-ischemic brain damage. Methods The 7 days old rats were randomly divided into three groups (n=24 in each group):sham-operated group,HIBD group and EPO-treated group.In sham-operated group,the median incision of neck was performed,and left common carotid artery was isolated,but not hypoxia-ischemia.In HIBD group,left common carotid artery was isolated and ligated,then the models were prepared under hypoxia for 2 h.In EPO-treated group,the model rats were instantly given single intraperitoneal injection of rhEPO (5 000 U /kg).The expression of VEGF and NF-κB were detected by immunohistochemistry at 6,12,24,72 hours after the operation. Results 1) Expression of VEGF was higher in HIBD group than in sham-operated group.Expression of VEGF was significantly higher in EPO-treated group than in sham-operated group and HIBD group at the same time (P<0.01).2) Expression of NF-κB was higher in HIBD group than in sham-operated group.Expression of NF-κB was higher in HIBD group than in EPO-treated group at the same time (P<0.01). Conclusion Erythropoietin can up-regulate expression of VEGF and reduce expression of NF-κB in neonatal rats after hypoxic-ischemic brain damage,which may be one of the mechanisms for protecting HIBD.
关键词
促红细胞生成素 /
血管内皮生长因子 /
核因子-κB /
缺氧缺血 /
新生大鼠
Key words
erythropoietin /
vascular endothelial growth factor /
nuclear factor kappa B /
hypoxia ischemia /
neonatal rats
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