雌激素联合依达拉奉对大鼠脑缺血再灌注的神经保护作用

The protective effect of estrogen combined with edaravone on the brain of rats with cerebral ischemia reperfusion

目的通过观察雌激素和依达拉奉对大鼠脑局灶性缺血再灌注损伤后ICAM-1、TNF-α表达、SOD活力和MDA、NO含量的影响,探讨雌激素联合依达拉奉对大鼠脑缺血再灌注损伤后的脑保护作用及其可能机制。方法选择健康雄性SD大鼠200只,随机分为5组,即假手术组(SO)、缺血再灌注组(I/R)、依达拉奉组(Ed)、雌激素组(Es)和雌激素联合依达拉奉组(C),每组40只。建立大鼠右侧大脑中动脉闭塞局灶性脑缺血再灌注模型,应用免疫组化法测定大鼠大脑皮质ICAM-1、TNF-α表达情况,用生化法测定各组脑缺血再灌注后SOD活力、MDA、NO含量。结果在I/R组缺血侧大脑皮质各个时间点ICAM-1和TNF-α的表达明显高于SO组和Ed组、Es组、C组(P<0.01)。Ed组各个时间点ICAM-1和TNF-α的表达明显低于Es组和C组(P<0.05)。Ed组、Es组、C组及SO组脑组织SOD活力均高于I/R组(P<0.05),脑组织MDA及NO含量显著低于I/R组(P<0.05)。C组NO、MDA含量低于Es组、Ed组,C组SOD活力高于Es组(P<0.05)。结论雌激素和依达拉奉能通过抑制TNF-α的激活、减少ICAM-1的表达,从而减轻神经元的炎性反应,起到保护大脑的作用;雌激素和依达拉奉能增强SOD活力、减少MDA及NO含量,改善自由基代谢,有效减轻局灶性脑梗死引起的缺血性损伤。二者联合应用效果更好。

Objective To investigate the neuroprotective effect of estrogen and edaravone by observing the influence of estrogen and edaravone on the expression of ICAM-1, TNF-α and the contents of malondialdehyde （MDA） ,nitric oxide （NO）as well as activity of superoxide dismutase （SOD） after local cerebral ischemia reperfusion in rats. Methods 200 male SD rats were enrolled and randomly divided into 5 groups：sham operation group （ SO group ）, ischemia reperfusion group （ I/R group ）, edaravone treatment group （ Ed group ）, estrogen treatment group （Es group ） and combined treatment group （group C ）, with 40 rats in each group. The animal models with local cerebral ischemia reperfusion were established by means of the occlusion of middle cerebral artery according to Longa＇ s methods. The expression levels of ICAM-1, TNF-α were detected by immunohistoehemistry, the contents of MDA, NO and SOD activities were determined by biochemistry method. Results The expression levels of ICAM-1 and TNF-α in I/R group at different time points were significantly higher than those in SO group,Ed group,Es group and C group（ P 〈0. 01 ）. The expression levels of ICAM-1 and TNF-αin Ed group were significantly lower than those in Es group and group C（ P 〈 0.05 ）at each time point. The SOD activities in Ed group, Es group, group C and SO group were significantly higher than those in I/R group （ P 〈 0.05 ） , however, the concentrations of MDA and NO in these groups were significantly lower than those in I/R group （ P 〈 0. 05 ）. The contents of NO, MDA in group C were lower than those in Es group and Ed group, however,which in group C were significantly higher than those in Es group （ P 〈 0.05 ）. Conclusion Estrogen and edaravone have neuroprotective effect by inhibiting the activation of TNF-α, reducing the expression of ICAM-1 so as to relieve inflammatory reaction of neuron. Estrogen and edaravone can enhance the activities of SOD, reduce the contents of MDA and NO, improve metabolism of free radicals so as to relieve effectively ischemic injury caused by local cerebral infarction. The effect of combined application of both drugs is more obvious.