摘要
背景:近年来研究发现托吡酯能阻断电压依赖性钠通道;增强γ氨基丁酸(Gamma-aminobutyricacid,GABA)能的活性;阻滞α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/海人藻酸(α-amino-3-hydroxy-5-methy-lisoxazole-4-propionicacid/kainicacid,AMPA/KA)型谷氨酸受体的作用,从而推测其有神经保护作用。目的:观察托吡酯对大鼠局灶脑缺血的神经保护作用。设计:完全随机设计、对照实验研究。地点与材料:地点为上海第二医科大学附属仁济医院神经生物实验室。健康雄性大鼠50只Sprague-Dawley,体质量280～350g,随机分为3组,购自中科院上海实验动物中心。干预:以腔内线栓法制作大鼠局灶脑缺血模型,将50只Sprague-Dawley大鼠单纯随机分为对照组(10只)、40mg/kg治疗组(20只)、80mg/kg治疗组(20只),在缺血30min后一次腹腔注射托吡酯,对照组注射生理盐水。主要观察指标:分别在4,24h后观察神经功能评分,24h后干/湿重法测定脑组织含湿量、氯化三苯基四氮唑(2,3,5-triphenyltetrazoliumchlo-ride,TTC)染色观察测定梗死体积百分比。结果:①24h后神经功能评分显示,无论是40mg/kg组(3.20±0.52)还是80mg/kg组(2.70±0.47),分别与4h(40mg/kg,3.90±0.31;80mg/kg,3.80±0.41)相比有非常显著(P<0.01)的差异,两治疗组24h的评分与对照组的?
BACKGROUND:Recent studies have found that topiramate(TPM) is capable of suppre ssing voltage-gated Na+channel,enhancing γ-aminobutyric acid(GABA) activity, and inhibiting α-amino-3-hydroxy -5-methylisoxazole-4-propionic acid(AMP A)/kainate (KA) type glutamic acid receptor-mediated effects, thereby deducing that it possesses neuroprotective activity. OBJECTIVE:To investigate the neuroprotective effects of TPM against focal isch emic brain damage in rats. DESIGN:Completely randomized controlled trial. SETTING and MATERIALS:This study was conducted in the Neurobiological Laborato ry of Renji Hospital affiliated to Shanghai Second Medical University.Fifty heal thy male SD rats weighing 280-350 g were purchased from Shanghai Experimental A nimal Center of Chinese Academy of Science. INTERVENTION:Focal brain ischemic models were successfully established in 50 S D rats by intravascular occlusion of the middle cerebral artery with nylon sutur e, and then randomly divided into control group(n=10) and two TPM treatment grou ps(n=20 in both groups).Thirty minutes after ischemia,the rats received intra-p eritoneal injection of either saline(control group) or TPM(in the treatment grou ps at the dose of 40 and 80 mg/kg,respectively). MAIN OUTCOME MEASURES:The neurological deficits were scored 4 and 24 hours fol lowing the ischemia respectively.The cerebral water content was measured 24 hour s after ischemia,and the infarction volume was determined by using 2,3,5-triphe nyltetrazolium chloride(TTC) staining. RESULTS:①The scores for neurological deficits in both 40 and 80 mg/kg TPM gro ups measured at 24 hours following the ischemia(3.20±0.52 and 2.70±0.47,respec tively) were significantly different from those at 4 hours after ischemia(3.90± 0.31 and 3.80±0.41;P< 0.01),and the scores at 24 hours were significantly lower than that of the control group(3.80±0.63,P< 0.05 and P< 0.01,respectively).②T he water contents of the affected hemisphere in 40 and 80 mg/kg TPM treatment gr oups were(81.98±0.78)%and(80.38±0.80)%respectively, significantly lower than that of the control group[(83.05±0.56)%;P< 0.05 and P< 0.01,respectively].③T he cerebral infarct volume, when compared with that in the control group[(41.40 ±3.36)%],was reduced to(38.00±4.26)%in 40 mg/kg TPM group(P=0.168 6),and to( 34.50±6.52)%in 80 mg/kg TPM group(P< 0.05). CONCLUSION:TPM produces neuroprotective effects to alleviate neurological defi cits,reduce cerebral edema, and even decrease infarct volume dose-dependently i n rat models of focal ischemic brain damage.
出处
《中国临床康复》
CSCD
2004年第13期2578-2580,共3页
Chinese Journal of Clinical Rehabilitation
