Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats.
Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats.
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DOI：
10.1371/journal.pone.0057870
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Chen G;Gong M;Yan M;Zhang X
挥发性麻醉药可诱导老年神经元变性和凋亡，但其机制尚不清楚，老年患者术后更易出现记忆障碍。因此，我们推测内质网应激介导的海马神经元凋亡可能在七氟醚致老年大鼠认知功能障碍的机制中发挥重要作用。将30只18月龄雄性SD大鼠分为两组：假麻醉组（在丙烯酸麻醉室中暴露于简单湿化的30 - 50%O2和N2平衡5 h）和七氟烷麻醉组（在相同湿化混合空气中接受2%七氟烷相同时间）。Morris水迷宫实验检测大鼠空间记忆能力。透射电镜观察海马超微结构。采用免疫组织化学和实时荧光定量PCR方法观察海马C/EBP同源蛋白（CHOP）和caspase-12的表达。TUNEL法检测神经元凋亡情况。Morris水迷宫实验显示七氟醚麻醉可引起老龄大鼠空间记忆障碍（P <0.05）。凋亡神经元浓缩，染色质聚集，核膜断裂，透射电子显微镜观察证实七氟烷组大鼠出现凋亡变性。七氟醚组大鼠海马CHOP、caspase-12表达增加，TUNEL阳性细胞数增加（P <0.05）。结果提示，七氟醚长期暴露可引起衰老大鼠神经元变性和认知功能障碍。内质网应激介导的神经元凋亡可能在七氟醚致衰老大鼠记忆障碍中起一定作用。
Elderly patients are more likely to suffer from postoperative memory impairment for volatile anesthetics could induce aging neurons degeneration and apoptosis while the mechanism was still elusive. Therefore we hypothesized that ER stress mediated hippocampal neurons apoptosis might play an important role in the mechanism of sevoflurane-induced cognitive impairment in aged rats. Thirty 18-month-old male Sprague-Dawley rats were divided into two groups: the sham anesthesia group (exposure to simply humidified 30–50% O2 balanced by N2 in an acrylic anesthetizing chamber for 5 hours) and the sevoflurane anesthesia group (received 2% sevoflurane in the same humidified mixed air in an identical chamber for the same time). Spatial memory of rats was assayed by the Morris water maze test. The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM). The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis. The apoptosis neurons were also assessed by TUNEL assay. The Morris water maze test showed that sevoflurane anesthesia induced spatial memory impairment in aging rats (P<0.05). The apoptotic neurons were condensed and had clumped chromatin with fragmentation of the nuclear membrane, verifying apoptotic degeneration in the sevoflurane group rats by TEM observation. The expressions of CHOP and caspase-12 increased, and the number of TUNEL positive cells of the hippocampus also increased in the sevoflurane group rats (P<0.05). The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats. The ER stress mediated neurons apoptosis may play a role in the sevoflurane-induced memory impairment in aging rats.
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