拉莫三嗪对新生鼠缺氧缺血性脑损伤的神经保护作用  

Neuroprotective effects of lamotrigine on hypoxic-ischemic brain damage in neonatal rats

作　　者：郭文超[1,2] 易咏红[1] 廖卫平[1] 孙卫文[1] 苏涛[1] 陆雪芬[1] 

机构地区：[1]广州医学院第二附属医院神经内科,广州医学院神经科学研究所,中山市人民医院神经内科510260 [2]中山市人民医院神经内科

出　　处：《中华神经科杂志》2005年第9期549-552,共4页Chinese Journal of Neurology

基　　金：广东省医学科学技术研究基金(A2002298)

摘　　要：目的研究拉莫三嗪(LTG)对缺氧缺血性脑损伤(HIBD)新生大鼠的神经保护作用,以及不同用药剂量和用药时间对该作用的影响。方法7日龄SD大鼠126只,除假手术组(14只)外均行左侧颈总动脉离断并置入密闭缺氧箱,制备HIBD动物模型。LTG治疗A组(56只)术后3h分别给予LTG5、10、20、40mg/kg,治疗B组(42只)术前1h和术后3、6h给予LTG20mg/kg腹腔注射,缺血缺氧组(14只)无治疗。用酶标法、免疫组化和原位末端标记(TUNEL)法,分别检测HIBD24h后血清神经元特异性烯醇化酶(NSE)浓度、大脑皮层NSE阳性细胞数以及大脑皮层和齿状回TUNEL阳性细胞数。结果与缺氧缺血组比较,10、20、40mg/kg LTG组TUNEL阳性细胞数显著减少;20mg/kg和40mg/kg LTG治疗组血清NSE的浓度显著降低[缺血缺氧组:(103·3±3·3)μg/ml,20mg/kg组:(51·2±2·5)μg/ml,40mg/kg组:(32·4±1·7)μg/ml],皮层NSE阳性细胞数则显著增高,40mg/kg组(78·3±6·5)比20mg/kg组(63·4±6·6)改变更显著。术前1h与术后3、6h给药组的血清NSE的浓度均显著降低,NSE及TUNEL阳性细胞数均显著性增高,术前1h组改变较术后3、6h给药组显著,3h与6h给药组间差异无统计学意义。结论LTG对HIBD新生大鼠可产生神经保护作用,作用疗效与用药时间和剂量有关。Objective To study the neuroproteetive effects of lamotrigine （LTG） on hypoxicischemic brain damage （HIBD） in neonatal rats, and the influence of administration time and dosage. Methods HIBD model was prepared by ligation of the left common carotid arteries for 2 hours in postnatal 7 days SD rats, and then having exposure of the rats to 8% of oxygen and 92% of nitrogen for 2 hours. The rats were divided into 4 groups： normal control group （n = 14）, hypoxic-iscbemic group （n = 14）, LTG- treated A and B groups. The rats in group A received intraperitoneal LTG 5, 10, 20 and 40 mg/kg （ n = 14 per each dose） at 3 hours after operation. The rats in group B received intraperitoneal LTG 20 mg/kg at 1 hour before the operation and at 3 hours, 6 hours after operation （n = 14 for each time point）. Twenty-four hours after operation, blood and brain samples were taken for serum neuron-specific enolase （ NSE ） test, immunohistochemical staining and in situ end labeling. Results The numbers of TUNEL positive neurons in dentate gyrus and cortex were significantly decreased in ≥ 10 mg/kg LTG-treated groups as compared with the hypoxic-iscbemic controls （ P 〈 0. 01 ）. The levels of serum NSE were significantly decreased and the numbers of NSE positive neurons were markedly increased in 20 mg/kg and 40 mg/kg LTG-treated groups compared with hypoxic-ischemic controls （ P 〈 0.01 ）. These changes were more significant shown in LTG pretreatment groups than in post-treated groups, and more apparent in group with LTG 40 mg/kg （78. 3 ± 6. 5） than in group with 20 mg/kg （63.4 ± 6.6）. Condusions LTG should be shown to have neuroprotective effects on hypoxic-ischemic brain damage in neonatal rats, which might be dose-related. LTG pretreatment should be more effective.

关 键 词：三嗪类 缺氧缺血 脑 神经保护药 磷酸丙酮酸水合酶 细胞凋亡 缺氧缺血性脑损伤 神经保护作用 神经元特异性烯醇化酶(NSE) 拉莫三嗪 TUNEL阳性细胞 

分 类 号：R722.12[医药卫生—儿科] R743.31[医药卫生—临床医学]