托吡酯对大鼠脑缺血再灌注后血清超氧化物歧化酶活性、丙二醛含量及神经功能的影响

Effects of Topiramate on activity of SOD,concentration of MDA in blood serum and on neurofunction after cerebral ischemia/perfusion in rats

目的探讨托吡酯(TPM)对大鼠脑缺血再灌注后血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和神经功能的影响。方法将SD大鼠随机分为缺血再灌注组、TPM组及假手术组;采用线栓法建立大鼠大脑中动脉闭塞模型,TPM组动物分别于插线和再灌注时腹腔注射TPM混悬液(8mg/ml,80mg/kg);各组术后24h时进行神经功能评分后处死动物。采用羟胺氧化法测定血清SOD活性及硫代巴比妥酸法测定血清MDA含量。结果血清SOD活性及MDA含量缺血再灌注组分别为(157.72±19.04)U/ml及(7.45±0.84)nmol/ml,TPM组分别为(171.25±15.72)U/ml及(6.10±0.98)nmol/ml,假手术组分别为(179.74±7.95)U/ml及(5.90±0.72)nmol/ml;与TPM组及假手术组相比,缺血再灌注组大鼠血清SOD活性明显降低,MDA含量明显升高(均P<0.05)。TPM组及假手术组间血清SOD活性和MDA含量差异无显著性。TPM组神经功能评分较缺血再灌注组有显著改善(P<0.05)。结论TPM能减少脑缺血再灌注大鼠脑组织中抗氧化酶的消耗,有效抑制氧自由基的产生及其毒性,具有减轻脑缺血神经功能障碍的作用。

Objective To investigate the effects of Topiramate （TPM） on activity of SOD and concentration of MDA in blood serum and the changes of the nerve function scores after cerebral ischemia/perfusion in rats. Methods Male Spraguc-Dawley rats were randomly divided into ischemia/perfusion group, TPM group and sham-operation group. Rat models of transient focal cerebral ischemia were made by 2 h occlusion of right middle cerebral artery occlusion and reperfusion for 24 h. Rats in TPM group were injected TPM （ 8 mg/m1,80 mg/kg） in the heginning of the artery occlusion and the reperfusion. The rats were sacrificed after they were evaluated by the nerve function deficiency scores. The activity of SOD and concentration of MDA in blood serum were measured. Results The activity of SOD and concentration of MDA in blood serum in ischcmia/perfusion group were （ 157.72±19.04） U/ml and （7.45±0. 84 ） nmol/ml, those in TPM group were （ 171.25± 15.72） U/ml and （（6.10±0. 98） nmol/ml, those in sham-operation group were （ 179.74±7.95 ） U/ml and （ 5.90±0. 72 ） nmol/ml. Compaired with shamoperation and TPM groups, the activity of SOD in ischemia/perfusion group was significantly lower, the concentration of MDA was obviously higher （ all P 〈 0.05 ）. But there were no significant difference between sham-operation and TPM groups. The neurological impairment scores in TPM group was obviously higher than ischcmia/perfusion group （P 〈 0. 05 ）. Conclusions TPM can decrease antioxidase waste and inhibit the cytotoxic effect of oxygen free radicals on cerebral neurons in cerebral ischemia/perfusion rats. TPM can recovery the neurofunction of rats with acute transient cerebral ischemia.