Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China.
Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6896-6904. doi: 10.26355/eurrev_201810_16159.
To explore the behavioral changes and the expressions of the A1 receptor (A1R) and balanced nucleoside transporter-1 (ENT1) in the brain of epileptic rats after activating the NF-E2-related factor 2 (Nrf2)-ARE signaling pathway.
Adult male Sprague-Dawley (SD) rats were randomly divided into normal control group, epilepsy group, and t-butylhydroquinone (tBHQ) group, with 10 rats in each group. Lithium-pilocarpine induced epilepsy model in rats was established. The first epileptic latency and seizure frequency within 1 hour were observed in each group using the Racine scoring system. HE (Hematoxylin and Eosin) staining was used to observe the pathological lesions in the brain tissue of each group. The expressions of A1R, ENT1, and relative genes in Nrf2-ARE pathway in rat hippocampus was detected by immunohistochemistry and Western blot.
Compared with rats in epileptic group, the first seizure latency was prolonged and the seizure frequency decreased in tBHQ group (p<0.05). The degree of brain lesions in tHBQ group was lighter than that of epilepsy group. ENT1 expression in rat hippocampus of epileptic group was significantly upregulated than that of normal control group and tBHQ group. Besides, the protein levels of A1R, Nrf2, HO-1, and ARE in rat hippocampus of epilepsy group markedly decreased compared with those of normal control group. However, protein expressions of A1R, Nrf2, HO-1, and ARE proteins in rat hippocampus of tBHQ group were markedly upregulated.
Activation of the Nrf2-ARE signaling pathway can reduce the pathological damage of rat hippocampal neurons, prolong the latency of seizures, and reduce the degree of epileptic seizure in rats.
探讨激活核因子 E2 相关因子 2（Nrf2）-抗氧化反应元件（ARE）信号通路后，癫痫大鼠大脑中的行为改变和 A1 受体（A1R）和平衡核苷转运体-1（ENT1）的表达。
成年雄性 Sprague-Dawley（SD）大鼠随机分为正常对照组、癫痫组和叔丁基对苯二酚（tBHQ）组，每组 10 只。采用氯化锂-匹罗卡品诱导大鼠癫痫模型。采用 Racine 评分系统观察各组大鼠的首次癫痫潜伏期和 1 小时内的癫痫发作频率。HE（苏木精和伊红）染色观察各组大鼠脑组织的病理损伤。采用免疫组化和 Western blot 检测大鼠海马组织 Nrf2-ARE 通路中 A1R、ENT1 和相关基因的表达。
与癫痫组大鼠相比，tBHQ 组大鼠的首次癫痫发作潜伏期延长，癫痫发作频率降低（p<0.05）。tBHQ 组大鼠的脑损伤程度较癫痫组大鼠减轻。与正常对照组和 tBHQ 组相比，癫痫组大鼠海马组织中 ENT1 的表达明显上调。此外，与正常对照组相比，癫痫组大鼠海马组织中 A1R、Nrf2、HO-1 和 ARE 的蛋白水平明显降低。然而，tBHQ 组大鼠海马组织中 A1R、Nrf2、HO-1 和 ARE 蛋白的表达明显上调。
激活 Nrf2-ARE 信号通路可减轻大鼠海马神经元的病理损伤，延长癫痫发作潜伏期，降低癫痫大鼠的癫痫发作程度。
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