β-七叶皂甙钠对大鼠局灶性脑缺血再灌注后NF-кB、ICAM-1、VCAM-1表达的影响

Effect of β-Sodium Aescinate on expressions of NF-кB,ICAM-1 and VCAM-1 in rat models of transient focal is-chemia-reperfusion

目的探讨大鼠局灶性脑缺血再灌注脑组织缺血区不同时间点NF-кB、ICAM-1、VCAM-1蛋白表达的变化,及β-七叶皂甙钠干预效果。方法采用大鼠大脑中动脉闭塞法(MCAO)制作局灶性脑缺血再灌注模型,用免疫组织化学方法观察大鼠脑缺血再灌注不同时间段,NF-кB、ICAM-1、VCAM-1蛋白的表达。并在大鼠于脑缺血前24h、1h及再灌注即刻分别腹腔给予β-七叶皂甙钠5mg/kg,2h MCAO,再灌注24h、48h后取脑,运用TTC染色测算脑梗死体积,免疫组化染色检测NF-кB、ICAM-1、VCAM-1蛋白表达,分析β-七叶皂甙钠的干预效应。结果(1)脑缺血后缺血区脑组织NF-кB及ICAM-1、VCAM-1表达均增加,NF-kB于再灌注后12～24h表达达高峰,Ⅰ- CAM-1于再灌注后24h表达达高峰,VCAM-1于再灌注后24～48h表达达高峰。(2)NF-кB的表达与血管内皮I- CAM-1、VCAM-1的表达呈正相关。(3)β-七叶皂甙钠能显著降低脑缺血再灌注后24h和48h缺血区NF-кB、ICAM- 1及VCAM-1的表达增加。(4)β-七叶皂甙钠能明显减轻脑缺血再灌注后的脑组织损伤,再灌注24h脑梗死体积减少41.8%。结论(1)脑缺血再灌注后NF-кB、ICAM-1、VCAM-1大量表达,这可能是脑缺血再灌注损伤机制之一。(2)脑缺血后NF-кB的活化可能与微血管内皮细胞ICAM-1、VCAM-1蛋白表达调控有关。(3)β-七叶皂甙钠能够减轻脑缺血后的脑组织损伤,有神经保护作用。

Objective To investigat rat transient focal ischemia-reperfusion with expressions of NF-κB,I- CAM-1 and VCAM-1 after different time of ischemia-reperfusion and explore intervening effects of β-Sodium Aescinate. Methods Rat models of transient focal ischemia-reperfusion were established by occluding the right middle cerebral artery（MCA）,using an intraluminal filament method. The expressions of NF-κB,ICAM-1 and VCAM-1 in cerebral ischemic territory after different time of ischemia-reperfusion were detected by immunohistochemistry way. 5mg/kg β-Sodium Aescinate was given peritoneally 24h and lh before ischemia and at the same time of reperfusion,respectively. We analyzed the effects of β-Sodium Aescinate on brain by evaluating the infarct volume and the expressions of NF-κB,ICAM-1 and VCAM-1 through TTC staining and immunohistochemistry 24h and 48h after reperfusion. Results （1） The expressions of NF-κB,ICAM-1 and VCAM-1 in ischemic territory increased after cerebral ischemia. NF-κB immunoreactivity peaked during .12～24h after reperfusion. ICAM-1 immunoreactivity peaked at 24h after reperfusion and VCAM-1 during 24～48h. （2） The expression of NF-κB was positively correlated with the expressions of ICAM-1 and VCAM-1. （3） β-Sodium Aescinate could decrease the expressions of NF-κB,ICAM-1 and VCAM-1 remarkably 24h and 48h after reperfusion. （4） β-Sodium Aescinate could obviously reduce the brain damage after ischemia-reperfusion,and the infarct volume was significantly reduced by 41.8% in the β-Sodium Aescinate-treated group compared with the control group. Conclusion （1） High expressions of NF-κB, ICAM-1 and VCAM-1 may play a key role in the cerebral ischemia-reperfusion injury. （2） The activation of NF-κB may be involved in the modulating mechanism of the expressions of ICAM-1 and VCAM-1. （3） β-Sodium Aescinate may reduce the brain damage after cerebral ischemia and has neuroprotective effects on brain.