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Abstract：
BACKGROUND: Epilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms.
METHODS: Lithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group.
RESULTS: First, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced. Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses. Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2.
CONCLUSIONS: The current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats\' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.
METHODS: Lithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group.
RESULTS: First, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced. Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses. Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2.
CONCLUSIONS: The current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats\' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.
摘要：
背景：癫痫是一种常见的神经系统疾病，具有挑战性的机制和治疗策略。本研究研究了喹吡罗对氯化锂毛果芸香碱诱导的癫痫大鼠的神经保护作用，并探讨了其可能的机制。
方法：氯化锂毛果芸香碱诱导大鼠癫痫模型，评价喹吡罗对癫痫发作症状和认知功能的影响。拉辛评分法,脑电图,采用Morris水迷宫试验评价癫痫组大鼠的癫痫发作程度和学习记忆功能。此外,免疫组织化学和Westernblot技术分析谷氨酸受体2(GluR2;GRIA2)蛋白表达水平和形态学变化,巴克斯，癫痫组大鼠海马中的BCL2。
结果：首先，经证实，癫痫组大鼠的症状与癫痫的特征一致。此外，这些大鼠在Morris水迷宫试验中表现出学习和记忆功能下降。此外,癫痫组大鼠海马GluR2基因和蛋白水平显著降低。喹哌罗治疗可显着延迟癫痫发作，并降低癫痫发作后的死亡率。此外，脑电图显示尖峰波的频率显着降低。在莫里斯水迷宫测试中，来自喹吡罗治疗组的大鼠表现出更短的到达平台的潜伏期和通过目标象限的交叉数量增加。网络药理学分析显示，喹吡罗与GluR2密切相关，并参与cAMP信号通路，可卡因成瘾,和多巴胺能突触.此外，免疫组织化学和Westernblot分析表明，喹吡罗治疗导致癫痫组大鼠海马中颗粒细胞的排列更密集，形态更规则。此外,喹吡罗处理降低了BAX的蛋白表达,增加了BCL2的蛋白表达。
结论：目前的研究表明，喹吡罗对氯化锂毛果芸香碱诱导的癫痫大鼠模型具有神经保护作用。此外,发现这种治疗不仅减轻了老鼠的癫痫症状，而且还提高了他们的学习和记忆能力。这种改善与GLUR2，BAX，和BCL2。这些发现为进一步研究喹吡罗的治疗潜力及其治疗癫痫的潜在机制提供了重要线索。
方法：氯化锂毛果芸香碱诱导大鼠癫痫模型，评价喹吡罗对癫痫发作症状和认知功能的影响。拉辛评分法,脑电图,采用Morris水迷宫试验评价癫痫组大鼠的癫痫发作程度和学习记忆功能。此外,免疫组织化学和Westernblot技术分析谷氨酸受体2(GluR2;GRIA2)蛋白表达水平和形态学变化,巴克斯，癫痫组大鼠海马中的BCL2。
结果：首先，经证实，癫痫组大鼠的症状与癫痫的特征一致。此外，这些大鼠在Morris水迷宫试验中表现出学习和记忆功能下降。此外,癫痫组大鼠海马GluR2基因和蛋白水平显著降低。喹哌罗治疗可显着延迟癫痫发作，并降低癫痫发作后的死亡率。此外，脑电图显示尖峰波的频率显着降低。在莫里斯水迷宫测试中，来自喹吡罗治疗组的大鼠表现出更短的到达平台的潜伏期和通过目标象限的交叉数量增加。网络药理学分析显示，喹吡罗与GluR2密切相关，并参与cAMP信号通路，可卡因成瘾,和多巴胺能突触.此外，免疫组织化学和Westernblot分析表明，喹吡罗治疗导致癫痫组大鼠海马中颗粒细胞的排列更密集，形态更规则。此外,喹吡罗处理降低了BAX的蛋白表达,增加了BCL2的蛋白表达。
结论：目前的研究表明，喹吡罗对氯化锂毛果芸香碱诱导的癫痫大鼠模型具有神经保护作用。此外,发现这种治疗不仅减轻了老鼠的癫痫症状，而且还提高了他们的学习和记忆能力。这种改善与GLUR2，BAX，和BCL2。这些发现为进一步研究喹吡罗的治疗潜力及其治疗癫痫的潜在机制提供了重要线索。
