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目的目前国内外鲜见托吡酯(TPM)对小儿慢性癫癎发作所致脑神经元损伤保护作用及发挥最佳保护作用的适宜剂量的研究;亦尚未发现TPM与叶酸(FA)合用对TPM神经元保护作用影响的相关报道。因此,取得TPM单药及伍用FA后对幼鼠慢性癫癎发作引起的脑神经元损伤的保护作用实验室证据将对儿科临床用药具有重要的指导意义。方法将3周龄雄性Wistar大鼠随机分为6组:阴性对照组、阳性对照组、TPM-20组、TPM-40组、TPM-80组和TPM-40+FA组。阳性对照组和TPM4个组先行戊四氮(PTZ)腹腔注射制造幼鼠慢性癫癎模型,再分别每日给予等量蒸馏水、TPM20mg/kg、40mg/kg、80mg/kg和TPM40mg/kg+FA5mg/kg灌胃;阴性对照组则先行生理盐水腹腔注射,再给予等量的蒸馏水灌胃。连续用药2个月。观察大鼠行为、血清神经元特异性烯醇化酶(NSE)及海马区病理改变。结果TPM4个组大鼠惊厥发作次数,血清NSE水平及海马区神经元死亡程度较阳性对照组明显减轻。阴性对照组、阳性对照组、TPM-20组、TPM-40组、TPM-80组、TPM-40+FA组的惊厥发作次数依次为:0,48.4±3.7,44.7±2.9,44.3±3.1,42.7±3.2,40.8±3.7次;血清NSE值依次为:18.72±2.95,35.71±5.97,27.40±6.40,24.79±6.22,21.47±6.87,22.55±7.02μg/L;海马CA3区坏死神经元细胞百分比依次为:(5.8±1.9)%、(72.2±9.8)%、(43.9±7.1)%、(25.9±5.5)%、(10.5±4.2)%、(16.1±4.8)%;海马CA1区坏死神经元细胞百分比依次为:(5.1±1.8)%、(65.6±8.1)%、(40.5±6.4)%、(23.1±5.2)%、(8.9±3.6)%、(14.9±4.3)%。结论TPM对幼鼠慢性癫癎发作引起的脑神经元损伤具有保护作用,该作用存在剂量效应,TPM80mg/(kg.d)保护作用最强;TPM伍用FA后,神经元保护作用加强。
OBJECTIVE Currently no protective effect of topiramate (TPM) on cerebral neuronal injury induced by chronic epileptic seizures in children and the optimal dosage of TPM have been studied. At the same time, no combination of TPM and folic acid (FA) Protection of the impact of the relevant reports. Therefore, obtaining TPM single drug and Wu FA after neuroprotective effect of neuronal damage caused by chronic epilepsy in young rats laboratory evidence will have important guiding significance for pediatric clinical medication. Methods Male Wistar rats of 3 weeks old were randomly divided into 6 groups: negative control group, positive control group, TPM-20 group, TPM-40 group, TPM-80 group and TPM-40 + FA group. The positive control group and the TPM4 group were injected with pentylenetetrazol (PTZ) intraperitoneally to make the model of chronic epilepsy in young rats. The rats were treated with TPM20mg / kg, 40mg / kg, 80mg / kg and TPM40mg / kg + FA5mg / kg gavage; negative control group was first saline injection, and then given the same amount of distilled water gavage. Continuous medication for 2 months. The behavior, serum neuron-specific enolase (NSE) and pathological changes in hippocampus were observed. Results The number of seizures, serum NSE level and neuronal death in hippocampus in TPM4 group were significantly lower than those in positive control group. The frequency of seizures in the negative control group, positive control group, TPM-20 group, TPM-40 group, TPM-80 group and TPM-40 + FA group were 0,48.4 ± 3.7,44.7 ± 2.9,44.3 ± 3.1, 42.7 ± 3.2, 40.8 ± 3.7 times; the serum NSE values were as follows: 18.72 ± 2.95,35.71 ± 5.97,27.40 ± 6.40,24.79 ± 6.22,21.47 ± 6.87,22.55 ± 7.02μg / L; the percentage of necrotic neurons in hippocampal CA3 area Were followed up as follows: (5.8 ± 1.9)%, (72.2 ± 9.8)%, (43.9 ± 7.1)%, (25.9 ± 5.5)%, (10.5 ± 4.2)%, (16.1 ± 4.8) The percentages of metaplastic cells were (5.1 ± 1.8)%, (65.6 ± 8.1)%, (40.5 ± 6.4)%, (23.1 ± 5.2)%, (8.9 ± 3.6)% and (14.9 ± 4.3)%, respectively. Conclusion TPM can protect neurons from neuronal injury induced by chronic epilepsy in young rats. The effect of TPM is dose-dependent. TPM at 80mg / (kg · d) has the strongest protective effect.