依达拉奉对大鼠颅脑创伤后神经元凋亡的影响

Effect of edaravone on neuronal apoptosis after traumatic brain injury in rats

目的探讨依达拉奉对大鼠颅脑创伤后神经元凋亡的影响和神经保护作用机制。方法 96只Wistar大鼠随机分为正常组、假手术组、模型组和药物组,参照Marmarou方法构建大鼠闭合型脑创伤模型;分别采用硫代巴比妥酸比色法(TBA)和羟胺法检测血清丙二醛(MDA)、超氧化物歧化酶(SOD)水平,免疫组织化学法检测Fas、门冬氨酸特异半胱氨酸蛋白酶-8(Caspase-8)的表达,原位末端标记技术法(TUNEL)检测神经元凋亡情况。结果模型组较正常组、假手术组MDA量显著增高(P<0.05);药物组较模型组MDA量显著降低(P<0.05);模型组较正常组、假手术组SOD量显著降低(P<0.05);药物组较模型组SOD量显著增高(P<0.05)。模型组较正常组、假手术组Fas、Caspase-8表达均显著增高(P<0.05);药物组较模型组Fas、Caspase-8表达均显著降低(P<0.05)。模型组较正常组、假手术组凋亡细胞显著增多(P<0.05);药物组较模型组凋亡细胞数显著减少(P<0.05)。结论依达拉奉可有效提高颅脑创伤后脑组织SOD量,降低MDA量,通过下调颅脑创伤后Fas介导的凋亡程序,以发挥对大鼠颅脑创伤后神经元的保护作用。

Objective To investigate the effect of edaravone on the neuronal apoptosis after traumatic brain injury in rats and its neuroprotective mechanism. Methods Forty-six Wistar rats were randomly divided into normal group,sham operation group,model group and drug group. The model of rat brain injury was established by Marmarou method; Serum malondialdehyde（ MDA） and superoxide dismutase（ SOD） were measured by TBA colorimetry and hydroxylamine method respectively. The expression of Fas and cysteine aspartic acid specific protease-8（ Caspase-8） was detected by immunohistochemistry. TUNEL method was used to detect neuronal apoptosis. Results Compared with the normal group and the sham operation group,the content of MDA in the model group was significantly higher（ P〈0.05）,the content of MDA in the drug group was significantly lower than that in model group（ P〈0.05）; Compared with the normal group and the sham operation group,the activity of SOD in the model group was significantly lower（ P〈0.05）,the activity of SOD in the treatment group was significantly higher than that in model group（ P〈0.05）. Compared with the normal group and the sham operation group,the expression of Fas and Caspase-8 in the sham operation group were significantly higher（ P〈0.05）. The expression of Fas and Caspase-8 in the treatment group was significantly lower than that in model group（ P〈0.05）; Compared with the normal group and the sham operation group,the number of apoptotic cells in the sham operation group were significantly increased（ P〈0.05）. The number of apoptotic cells in the drug group was significantly lower than that inmodel group（ P〈0.05）. Conclusion Edaravone can effectively increase the activity of SOD and reduce the content of MDA in brain tissue after traumatic brain injury,the mechanism may contribute to down-regulate Fas-mediated apoptosis after traumatic brain injury.