GLYCYRRHIZIN ATTENUATES ISOFLURANE-INDUCED COGNITIVE DEFICITS IN NEONATAL RATS VIA ITS ANTI-INFLAMMATORY ACTIVITY
GLYCYRRHIZIN ATTENUATES ISOFLURANE-INDUCED COGNITIVE DEFICITS IN NEONATAL RATS VIA ITS ANTI-INFLAMMATORY ACTIVITY
复制标题
甘草甜素通过其抗炎活性减轻异氟烷引起的新生大鼠认知缺陷
DOI：
10.1016/j.neuroscience.2015.11.001
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发表时间：
2016-03-01
期刊：
影响因子：
3.3
通讯作者：
Luo, A.
中科院分区：
文献类型：
--
作者：
Wang, W.;Chen, X.;Luo, A.
接触异氟烷等全身麻醉剂的儿童可能会增加认知障碍的风险。最近的研究表明，这种认知能力下降与新生啮齿动物海马体的神经炎症有关。甘草酸是一种天然化合物，可用于治疗炎症和神经退行性疾病。因此，我们的目的是研究甘草甜素对异氟醚诱导的新生大鼠认知缺陷和海马神经炎症的影响。 7 日龄大鼠暴露于 1.8% 异氟烷 4 小时。在异氟烷或对照气体暴露前 30 分钟腹腔注射盐水和甘草酸溶液。使用莫里斯水迷宫 (MWM) 任务检查异氟烷和甘草甜素治疗对记忆表现的影响。通过蛋白质印迹法测定高迁移率组盒 1 (HMGB1)、NF kappa B、Bcl-2、Bax 和裂解（活性）caspase-3 的蛋白表达。采用酶联免疫吸附法（ELISA）检测TNF-α和IL-1β蛋白水平。 ELISA 和 Western blot 结果表明，甘草甜素可减弱异氟醚诱导的新生大鼠海马促炎细胞因子（TNF-α 和 IL-1β）的增加以及 HMGB1/NF kappa B 信号通路的激活。此外，甘草甜素治疗可以预防新生儿接触异氟烷引起的空间记忆缺陷。与这些观察结果一致，我们发现甘草酸减轻了异氟烷诱导的新生大鼠海马神经细胞凋亡以及 PSD-95 和 SNAP-25 的下调。这些结果表明，甘草甜素可能是一种潜在的治疗剂，用于治疗新生儿全身麻醉药引起的发育神经毒性和随后的认知能力下降。 (C) 2015 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Children exposed to general anesthetics such as isoflurane are maybe at an increased risk of cognitive impairment. Recent studies have indicated that this kind of cognitive decline is associated with neuroinflammation in the hippocampus of neonatal rodents. Glycyrrhizin is a naturally available compound for the treatment of inflammatory and neurodegenerative diseases. We therefore aimed to investigate the effects of glycyrrhizin on the isoflurane-induced cognitive deficits and hippocampal neuroinflammation in the neonatal rats. Seven day-old rats were exposed to 1.8% isoflurane for 4 h. Saline and glycyrrhizin solution was injected intraperitoneally 30 min prior to isoflurane or control gas exposure. The effects of isoflurane and glycyrrhizin treatment on memory performance were examined using Morris Water Maze (MWM) task. The protein expression of high-mobility group box 1 (HMGB1), NF kappa B, Bcl-2, Bax and cleaved (active) caspase-3 were determined by Western blot assay. The protein levels of TNF-alpha and IL-1 beta were detected by enzyme-linked immunosorbent assay (ELISA). The combination of ELISA and Western blot results showed that glycyrrhizin attenuated isoflurane-induced increases of pro-inflammatory cytokines (TNF-alpha and IL-1 beta) and activation of HMGB1/NF kappa B signaling pathway in the hippocampus of neonatal rats. Furthermore, glycyrrhizin treatment prevented the deficits in spatial memory induced by neonatal exposure to isoflurane. Consistent with these observations, we found that glycyrrhizin alleviated isoflurane-induced neuroapoptosis and down-regulations of PSD-95 and SNAP-25 in the hippocampus of neonatal rats. These results suggest that glycyrrhizin may be a potential therapeutic agent for developmental neurotoxicity and subsequent cognitive decline induced by neonatal exposure to general anesthetics. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.