OBJECTIVE(S) Although the available therapeutic agents alleviate the symptoms in patients with temporal lobe epilepsy (TLE), these antiepileptic drugs do not provide adequate control of seizures in 30-40% of patients. This study was conducted to evaluate anti-epileptic effects of simultaneous inhibition of dipeptidyl peptidase-4 and P2 × 7 purinoceptors in Kainate treated rats. MATERIALS AND METHODS Brilliant Blue G )BBG(, linagliptin )lin( and lin + BBG were administrated 30 min prior to induction of the intrahippocampal kainate model of epilepsy in male Wistar rats. In the case of valproic acid group, the animals intraperitoneally received valproic acid for 7 consecutive days prior to induction of the model. We carried out histological evaluations, monitoring of behavior, recording of intracranial electroencepholography (IEEG), and determination of astrogliosis and DNA fragmentation using ELISA methods. RESULTS Our results showed that BBG and lin combination therapy had better effects on decrease in astrogliosis, DNA fragmentation and cognitive disturbances than ones whereas its effects on neuronal survival and seizure severity was similar to only BBG or lin. Likewise, the effects of lin + BBG on decrease in DNA fragmentation and cognitive disturbances were better than valproic acid group. CONCLUSION Our findings suggest that simultaneous inhibition of dipeptidyl peptidase-4 and P2 × 7 purinoceptors might more efficiently provide protection against progression of the kainate-induced TLE in rats.

中文翻译：

---

二肽基肽酶 4 和 P2X7 嘌呤受体抑制剂的联合治疗在大鼠中产生抗癫痫作用

目标虽然可用的治疗药物可缓解颞叶癫痫 (TLE) 患者的症状，但这些抗癫痫药物不能充分控制 30-40% 的患者的癫痫发作。本研究旨在评估同时抑制二肽基肽酶-4 和 P2 × 7 嘌呤受体在红藻氨酸处理的大鼠中的抗癫痫作用。材料与方法 雄性Wistar大鼠海马红藻氨酸癫痫模型诱导前30分钟给予亮蓝G)BBG(、利格列汀)lin(和lin+BBG)。模型诱导前连续 7 天酸。我们进行了组织学评估，行为监测，颅内脑电图 (IEEG) 记录，使用 ELISA 方法测定星形胶质细胞增生症和 DNA 片段化。结果 我们的结果表明，BBG 和 lin 联合治疗在减少星形胶质细胞增生、DNA 断裂和认知障碍方面的效果优于那些，而其对神经元存活和癫痫严重程度的影响与仅 BBG 或 lin 相似。同样，lin + BBG 在减少 DNA 断裂和认知障碍方面的效果优于丙戊酸组。结论 我们的研究结果表明，同时抑制二肽基肽酶-4 和 P2 × 7 嘌呤受体可能更有效地防止大鼠红藻氨酸诱导的 TLE 进展。DNA 碎片和认知障碍比那些，而其对神经元存活和癫痫严重程度的影响仅与 BBG 或 lin 相似。同样，lin + BBG 在减少 DNA 断裂和认知障碍方面的效果优于丙戊酸组。结论 我们的研究结果表明，同时抑制二肽基肽酶-4 和 P2 × 7 嘌呤受体可能更有效地防止大鼠红藻氨酸诱导的 TLE 进展。DNA 碎片和认知障碍比那些，而其对神经元存活和癫痫严重程度的影响仅与 BBG 或 lin 相似。同样，lin + BBG 在减少 DNA 断裂和认知障碍方面的效果优于丙戊酸组。结论 我们的研究结果表明，同时抑制二肽基肽酶-4 和 P2 × 7 嘌呤受体可能更有效地防止大鼠红藻氨酸诱导的 TLE 进展。