右美沙芬对家兔急性脑外伤后脑组织c-fos蛋白和神经元的影响

Changes of C-fos expression and neurocyte necrosis after dextromethorphan therapy for rabbits with acute brain injury

目的 :探讨NMDA受体拮抗剂———右美沙芬 (DM)对家兔急性脑外伤后脑组织c fos蛋白和神经元的作用。方法 :成年雄性家兔 2 4只。随机抽取 4只作为对照组。余 2 0只利用颅脑外伤自由落体打击器造成一侧脑外伤 ,伤后动物被随机平均分为外伤组和治疗组。治疗组动物在外伤后立即腹腔注射DM 50mg/kg,对照组和外伤组在伤后立即腹腔注射等量生理盐水。伤后 6h后处死各组动物 ,取左顶叶伤灶及周围皮层制作切片。采用免疫组化方法及计算机图像分析设备检测伤灶及周围脑组织c fos蛋白的表达 ,计数坏死神经元。结果 :对照组未见c fos阳性细胞的表达。外伤组可见大量的片状棕黄色c fos蛋白阳性细胞 ,阳性产物主要分布在胞浆内 ,少数存在于胞核中 ,部分核仁也呈深褐色。治疗组可见弥散分布的阳性细胞 ,呈点状或小片状棕褐色颗粒 ,c fos蛋白阳性细胞数明显减少 ,分布较稀疏 ,也主要表达于胞浆内。DM治疗后 6h单位面积内c fos蛋白阳性细胞数 (5 .8± 2 .0 )较外伤组 (1 9.8± 3 .6)显著减少 ,而灰度值 (1 1 3 .3± 6 .4)较外伤组 (74.3± 6 .2 )明显增加 ,坏死神经元百分数 38.2 %也较外伤组的 62 .8%低 (P均 <0 .0 1 )。结论 :兔脑外伤后右美沙芬治疗可抑制继发性损害因子c fos蛋白的表达 。

Aim:To study the expression of c fos protein and neurocyte necrosis in rabbit model of traumatic brain injury treated with dextromethorphan (DM).Methods:Control group was 4 rabbits without injury (group A, n =4).Twenty adult male rabbits were subjected to a lateral traumatic brain injury and randomly allocated into injury group (group B, n =10) and treatment group(group C, n =10) after injury.Group A and group B were given normal saline,and group C were treated with DM 50 mg/kg immediately after injury.All animals were sacrificed 6 hours post injury. Immunohistochemistry and computer image analysis system were used to detect the expression of c fos protein, and the number of necrotic neurocytes was counted at and around the impact site.Results:There was no expression of c fos protein in group A.Expression of c fos protein and the number of necrotic neurocytes in group C were significantly lower than those of group B ( P <0.01,respectively).Conclusions:The treatment of DM after brain injury can inhibit the expression of c fos protein and reduce the number of necrotic neurocytes. The brain protection of DM may associate with its inhibiting c fos protein expression.