促红细胞生成素对大鼠脑出血炎症反应的抑制作用及机制*

关键词：脑出血  炎症反应  核因子κB  抑制因子κBα  促红细胞生成素

Keywords:intracerebral hemorrhage  inflammatory reaction  nuclear factor-Kappa B  inhibitory factor-Kappa B alpha  erythropoietin

摘要：

      目的： 研究实验性大鼠脑出血后血肿周围核因子-κB (NF-κB)及其抑制因子κBα(IκBα)的表达，以及促红细胞生成素（EPO）对其干预作用，探讨EPO对出血性脑炎症反应的作用及机制。方法：将126只大鼠随机分为假手术组、脑出血组、EPO干预组。每组各42只，分别为术后第3、6、12、24、48、72小时和第7天亚组，每亚组各6只。采用大鼠尾动脉自体不凝血 50 μl注入尾状核区建立脑出血模型，分别在不同时间点断头取脑，连续切片作NF-κB 及IκBα免疫组化染色；观察各组各时间点NF-κB、 IκBα蛋白的表达并进行分析比较。结果：脑出血第6小时后NF-κB 及IκBα表达增高，第24小时明显增高，第72小时达到高峰，各时间点与假手术组比较差异均有显著性(P＜0.01)。EPO干预后NF-κB表达明显降低，与脑出血组比较有显著性差异(P＜0.01)；经EPO干预后IκBα表达显著增多,与脑出血组比较有显著性差异(P＜0.01)。结论：脑出血周围NF-κB及IκBα表达均有增多，EPO通过抑制NF-κB表达、促进IκBα表达抑制炎症反应从而起到神经保护作用。

Abstract:

      Objective:To investigate the expressions of nuclear factor-kappa B(NF-κB) p50 and inhibitory factor -kappa B alpha(IκBα) in the amph-hematoma of rats with experimental intracerebral hemorrhage and the effects of erythropoietin(EPO) on them, to study the depressant effects and mechanism of EPO to inflammatory reaction of intracerebral hemorrhage. Method: One hundred and twenty-six rats were randomly divided into 3 groups, i.e. sham operation group (SOG), intracerebral hemorrhage group(IHG) and EPO group (EPOG).There were forty-two rats in each group, and seven subsets respectively in this three groups, i.e. the 3rd,6th,12th,24th,48th and 72nd h and 7th d subsets six rats in each subset. Autologous blood 50μl were injected into the right caudate nucleus in rats to make an model of intracerebral hemorrhage and rats were decapitated to obtain brains in different time points. Then, serial sections were made and the expressions of NF-κB p50 and IκBα of these rats were detected with immunohistochemical assay and dependence assay in seven time points. Result: The expressions of NF-κBp50 and IκBα up-reguleted at the 6th h after operation, up-regulated significantly on the 24th h, getting to the peak level on the 72nd h. Compared with SOG the expression of NF-κB in IHG upregulated significantly (P<0.01). The expression of NF-κB in EPOG were lower than that in IHG(P<0.01). The expression of IκBα up-regulated obviously in the rats of EPOG(P<0.01). Conclusion: The expressions of NF-κB and IκBα up-regulated in the amph-hematoma in rats with experimental intracerebral hemorrhage. EPO may possess potential neuro-protective effect through inhibiting the expression of NF-κB and enhancing the expression of IκBα to depressant inflammatory reaction.