生酮饮食对海藻酸致癎大鼠海马突触重建和GluR5 表达的影响

目的探讨生酮饮食对海藻酸致大鼠海马突触重建和G luR5表达的影响机制。方法以海藻酸(KA)致的幼鼠为研究对象,采用Timm′s染色和尼氏染色,观察经不同饮食处理的动物海马结构和癫行为的变化;并用W estern B lot和RT-PCR法检测海马G luR5及其mRNA的表达。结果生酮饮食组动物自发性反复惊厥的次数(1.40±1.03)次,明显少于正常饮食组(7.36±3.75)次。KA致大鼠海马齿状回内分子层异常Timm′s染色颗粒的平均A值均显著高于非致组,但生酮饮食组和正常饮食组间则无明显差异;各组动物CA3区锥体细胞层及始层的Timm′s染色颗粒以及海马门区和CA1、CA3区神经元的平均A值未见明显差异。KA致后生酮饮食组大鼠海马G luR5的表达[(189.38±40.03)/mg总蛋白]明显高于正常饮食组[(128.79±46.51)/mg总蛋白],但两组间G luR5mRNA比较,差异无统计学意义。结论苔藓纤维发芽可能是KA致动物癫产生的原因,酮食疗法对KA致大鼠确有抗癫作用,其抗癫机制可能与增加幼年大鼠CA1区中间神经元G luR5的表达,使海马内抑制性突触传递增强,进而阻止癫活动扩散有关。

Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5 expression in kainic acid induced rat model of epilepsy

OBJECTIVE: Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. The aim of the study was to reveal the possible mechanism from the view points of synaptic reorganization and GluR(5) expression in hippocampus. METHODS: Epilepsy was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all control animals were fed with normal rodent chow, whereas experimental rats were fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were recorded. Mossy fiber sprouting and neuron damage in hippocampus were investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus. RESULTS: KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly higher in KA induced animals than that in saline control animals but it was similar in different diet fed groups. No significant differences were found in the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus, CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg pro] had significantly higher GluR(5) expression in hippocampus than control diet-fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same. CONCLUSION: Mossy fiber sprouting may be responsible for epileptogenesis in KA induced model and KD can suppress seizures in these animals. KD may upregulate young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased inhibition to prevent the propagation of seizure.