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目的探讨托吡酯(TPM)联合叶酸(FA)对慢性癫幼鼠海马CA3区神经元线粒体超微结构损伤的影响。方法将3周龄雄性Wistar大鼠随机分为阴性、阳性对照组、TPM组和TPM加FA组。予各组大鼠戊四氮(PTZ)腹腔注射,制造慢性癫模型,分别予等量蒸馏水、TPM40mg/(kg·d)和TPM40mg/(kg·d)加FA5mg/(kg·d)灌胃;阴性对照组先行9g/L盐水腹腔注射,再予等量的蒸馏水灌胃。连续用药2个月。观察各组行为学表现及海马CA3区神经元线粒体的超微结构。结果TPM和TPM加FA组大鼠惊厥发作次数及海马CA3区神经元线粒体的超微结构损伤程度较阳性对照组明显减轻。阳性对照、TPM和TPM加FA组的惊厥发作次数依次为:(48.4±3.7)、(44.3±3.1)、(40.8±3.7)次,3组间差异有统计学意义(Pa<0.01);阴性对照、阳性对照、TPM、TPM加FA组海马CA3区神经元线粒体的超微结构损伤程度依次为(0.34±0.09)、(3.76±0.28)、(2.85±0.21)、(2.09±0.31)级,4组间差异有统计学意义(Pa<0.01)。结论TPM对慢性癫发作所致的海马神经元线粒体损伤有保护作用,FA可加强TPM的线粒体保护作用。
Objective To investigate the effects of topiramate (TPM) combined with folic acid (FA) on the mitochondrial ultrastructure damage of hippocampal CA3 neurons in chronic epileptic seizures. Methods Three weeks old male Wistar rats were randomly divided into negative control group, TPM group and TPM plus FA group. Rats in each group were intraperitoneally injected with pentylenetetrazole (PTZ) to make a chronic epileptic model. The animals were treated with the same amount of distilled water, TPM40mg / (kg · d) and TPM40mg / (kg · d) plus FA5mg / (kg · d) Stomach; negative control group first 9g / L saline intraperitoneal injection, and then an equal amount of distilled water gavage. Continuous medication for 2 months. The behavioral findings and the ultrastructure of mitochondria in hippocampal CA3 area were observed. Results The frequency of seizure and the ultrastructural damage of mitochondria in hippocampal CA3 neurons in TPM and TPM plus FA groups were significantly lower than those in positive control group. The frequency of seizures in the positive control group, TPM group and TPM plus FA group was (48.4 ± 3.7), (44.3 ± 3.1) and (40.8 ± 3.7) times, respectively. There were significant differences among the three groups (Pa0.01) The ultrastructural damage of mitochondria in the hippocampal CA3 region of the control, positive control, TPM, TPM and FA groups were (0.34 ± 0.09), (3.76 ± 0.28), (2.85 ± 0.21) and (2.09 ± 0.31) The difference between the 4 groups was statistically significant (Pa <0.01). Conclusion TPM can protect the hippocampal neurons from mitochondrial damage induced by chronic epileptic seizures. FA may enhance the mitochondrial protective effect of TPM.