1,6-二磷酸果糖对反复热性惊厥大鼠海马区超微结构损伤保护作用的研究

Protective effect of fructose 1,6-diphosphate against ultrastructural damage in the hippocampus of rats with repeated febrile seizures

摘要:

目的：1，6-二磷酸果糖（FDP）作为细胞代谢的能量物质已被证实在辅助治疗缺氧缺血性脑病及心肌受损性疾病方面具有重要作用。该研究探讨FDP对大鼠热性惊厥性海马超微结构损伤是否具有保护作用。方法：36只21日龄雄性SD大鼠均分为热性惊厥组（FS），高剂量果糖干预组（HD）及低剂量果糖干预组（LD）。水浴法建立热性惊厥模型；高、低剂量果糖干预组于惊厥前30 min各腹腔注射FDP 50 mg/100 g及25 mg/100 g大鼠体重；而FS组腹腔注射相同体积的0.9%氯化钠溶液。应用透射电镜分别观察海马CA1区神经元、细胞器的病理超微结构改变和神经突触参数变化特征。结果：果糖干预组在神经元变性坏死、线粒体肿胀、内质网脱颗粒及高尔基体扩张等方面较FS组减轻，差异有显著性。果糖干预组同FS组相比，脑海马CA1区神经突触间隙缩窄（F=7.29，P<0.01），突触后致密物质厚度增加（F=12.47，P<0.01），突触活性带长度延长（F=14.75，P<0.01），突触界面曲率增加（F=3.77，P<0.05），差异有显著性。在改善上述超微结构损伤方面，HD与LD组比较差异无显著性。结论：FDP可以减轻反复热性惊厥大鼠海马区超微结构受损程度，但有效而适宜的用药剂量仍需进一步探讨。

Abstract:

OBJECTIVE: Fructose-1, 6-diphosphate (FDP), serving as a cellular energy substance, has shown its roles in the treatment of hypoxic-ischemic encephalopathy and myocardial damage. The present study aimed at exploring the potentiality of the protective effect of FDP against ultrastructural damage of the hippocampus caused by febrile seizures (FS) in rats. METHODS: Thirty-six 21-day-old male Sprague-Dawley rats were randomly divided into three groups: untreated FS (control), high-dose FDP-treated FS and low-dose FDP-treated FS. FS were induced by hyperthermal bath. Thirty minutes before FS induction, rats in the high-dose and low-dose FDP-treated groups received a peritoneal injection of FDP at a dosage of 50 and 25 mg per 100 g of body weight respectively, whereas the same volume of 0.9% sodium chloride solution were injected to the rats in the control group. Transmission electron microscopy was used to examine the ultrastructural pathologic changes of neurons and organelles as well as the features of synaptic morphological parameters in the hippocampal CA1 area. RESULTS: Neuronal degeneration and necrosis, mitochondria swelling, polyribosomes disaggregation from endoplasmic reticula, and golgiosomes dilation in the hippocampal CA1 area in the two FDP intervention groups were less severe compared with the control group. FDP treatment resulted in significant increases in postsynaptic density thickness (F=12.47, P<0.01), synaptic active zone length (F=14.75, P<0.01) and synaptic interface curvature (F=3.77, P<0.05), as well as a shorter interspace of neural synapses (F=7.29, P<0.01) when compared with the control group. There were no significant differences in the ultrastructural changes between the two FDP treatment groups. CONCLUSIONS: FDP can ameliorate ultrastructural damage in the hippocampus caused by FS in rats. However, further research is warranted for a reasonable and effective dosage of FDP.