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维生素D可保护大鼠免受与海藻酸和戊四氮诱导的癫痫发作相关的海马细胞凋亡。

Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats.

作者信息

Şahin Sevim, Gürgen Seren Gülşen, Yazar Uğur, İnce İmran, Kamaşak Tülay, Acar Arslan Elif, Diler Durgut Betül, Dilber Beril, Cansu Ali

机构信息

Department of Pediatric Neurology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.

Department of Histology and Embriyology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.

出版信息

Epilepsy Res. 2019 Jan;149:107-116. doi: 10.1016/j.eplepsyres.2018.12.005. Epub 2018 Dec 15.

Abstract

OBJECTIVES

The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epileptic patients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats.

METHODS

Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method.

RESULTS

BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001).

CONCLUSION

This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.

摘要

目的

海马体在癫痫患者以及由兴奋性毒性药物引发癫痫的动物中易受损伤。维生素D对与癫痫相关的海马体细胞凋亡的影响尚未见报道。然而,癫痫患者维生素D缺乏症的风险增加,这很可能是抗癫痫药物作用的结果。因此,在本研究中,旨在通过使用戊四氮(PTZ)和 kainic 酸(KA)处理大鼠,评估维生素D对与癫痫相关的海马体细胞凋亡的影响。

方法

5.5周龄的雄性Sprague Dawley大鼠随机分为六组:对照组、维生素D组、PTZ组、KA组、PTZ + 维生素D组和KA + 维生素D组。接受维生素D的组除标准饮食外,每天给予500 IU/kg维生素D,持续两周。在此期间结束时,对癫痫组大鼠应用PTZ和KA引发癫痫。给予PTZ和KA后24小时,将大鼠断头。在海马区,通过TUNEL法评估细胞凋亡,通过免疫组化法评估脑源性神经营养因子(BDNF)、Bax、半胱天冬酶 - 3和c - fos的激活情况。

结果

与PTZ组和KA组相比,在给予PTZ和KA之前用维生素D预处理的组的海马神经元中,BDNF水平升高,而c - fos、Bax和半胱天冬酶 - 3水平降低(所有p < 0.0001)。与PTZ组和KA组相比,维生素D显著减少了这些大鼠中的凋亡细胞数量(p < 0.0001)。

结论

本研究表明维生素D对PTZ和KA诱导的大鼠海马体细胞凋亡具有神经保护作用。通过本研究提示,将维生素D水平维持在正常范围内可能对癫痫患者,尤其是儿童有益。

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