右美沙芬治疗对兔急性脑外伤保护作用的研究

Protective effects of dextromethorphan therapy on rabbits with acute brain injury

目的 应用N -甲基天冬氨酸 (NMDA)受体拮抗剂右美沙芬 (DM)治疗兔脑外伤 ,并检测伤灶及其周围脑组织热休克蛋白 70 (HSP70 )表达及坏死细胞数的变化 ,探讨DM治疗对脑外伤后脑保护作用的机制。 方法 成年雄性家兔利用颅脑外伤自由落体打击器造成一侧脑外伤模型 ,伤后动物被分为治疗 6h组、7d组 ,外伤 6h组、7d组及对照 6h组、7d组 ,治疗组动物在外伤后立即给予腹腔注射右美沙芬治疗 ,剂量为 5 0mg·kg- 1 d- 1 ,外伤组和对照组给予腹腔注射等渗盐水 10ml d ,分别在伤后 6h、7d致死各组动物 ,采用免疫组化方法及计算机图像分析检测伤灶及周围脑组织HSP70的表达及坏死细胞数。 结果 对照组未见HSP70阳性细胞的表达。外伤后 ,伤灶及其周围可见大量HSP70表达。治疗组损伤灶及其周围的神经元HSP70表达较外伤组显著增加 ,而坏死神经元数目则显著减少。 结论 兔脑外伤后DM治疗可诱导内源性保护因子HSP70的表达增高 ,提高神经元对脑外伤后继发性损伤的耐受性 。

Objective To observe the expression of HSP70 proteinand necrotic neurocytes in rabbit model of traumatic brain injury treated with dextromethorphan (DM) so as to study the protective effects of DM on rabbits after brain injury. Methods Forty adult male rabbits were subjected to a lateral traumatic brain injury and divided into 6 groups after injury: treatment 6 hours (Group A) and 7 days (Group B); injury 6 hours (Group C) and 7 days (Group D); control 6 hours (Group E) and 7 days (Group F). Groups A and B were treated with DM (50 mg·kg 1 ·d 1 ) immediately after injury. Groups C, D, E and F were treated only with normal saline (NS) (10 ml/d) . The rabbits in the Groups C and D were sacrificed at the 6th hour, that in the Groups E and F sacrificed at the 7th day. Immunohistochemistry and computer image analysis system were used to detect the expression of HSP70 protein; and the number of necrotic neurocytes was counted in and around the impact site. Results There was no expression of HSP70 in the control groups. Expression of HSP70 protein could be seen in the Groups C and D. Compared with the Groups C and D, the expression of HSP70 protein was significantly increased in the Groups A and B. The necrotic neurocytes decreased obviously. Conclusions The treatment of DM can induce the expression of HSP70 protein, enhance the endurance of neurons to secondary brain injury after brain injury and hence increase the survival rate of neurons.