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| 米诺环素对异氟醚麻醉后老年大鼠认知功能和海马炎症反应的影响 |
| Effects of minocycline on neurocognitive impairment and hippocampal inflammatory response after isoflurane anesthesia in old rats |
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| DOI：10.12089/jca.2018.11.016 |
| 中文关键词: 异氟醚 米诺环素 老年大鼠 认知功能 炎性因子 |
| 英文关键词: Isoflurane Minocycline Old rats Cognitive function Inflammatory cytokines |
| 基金项目:国家自然科学基金面上项目(81271223) |
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| 中文摘要: |
目的 探讨米诺环素预处理对老年大鼠吸入异氟醚后认知功能和海马炎症反应的影响。
方法 健康雄性SPF级SD大鼠48只, 约20月龄, 体重350～400 g, 随机分为3组: 生理盐水组(NS组)、异氟醚组(Iso组)、米诺环素预给药组(M组), 每组16只。NS组腹腔注射等容量生理盐水; Iso组大鼠开始吸入2.5%异氟醚3 min, 随后1.5%异氟醚麻醉维持4 h; M组于吸入异氟醚前30 min腹腔注射米诺环素50 mg/kg, 余同Iso组。所有大鼠麻醉结束后24 h立即进行认知功能测试, 包括Morris水迷宫和旷场实验测试, 认知功能测试完毕后立即处死大鼠, 取海马组织, 采用ELISA法测定大鼠海马IL-1、IL-6、TNF-α的浓度。
结果 与NS组比较, Iso组第2、3和4天逃避潜伏期明显延长(P<0.05), 第5天平台象限停留时间明显缩短、穿越平台象限次数明显减少(P<0.05), 第1、2和3天中心区停留时间明显缩短(P<0.05)。与Iso组比较, M组第2、3和4天逃避潜伏期明显缩短(P<0.05), 第5天平台象限停留时间明显延长、穿越平台象限次数明显增多(P<0.05), 第1、2和3天中心区停留时间明显延长(P<0.05)。与NS组比较, Iso组海马IL-1、IL-6、TNF-α浓度明显升高(P<0.05), 与Iso组比较, M组海马IL-1、IL-6、TNF-α浓度明显降低(P<0.05)。NS组和M组不同时点各指标差异无统计学意义。
结论 米诺环素预处理可减轻异氟醚麻醉所致老年大鼠认知功能障碍, 其机制可能与抑制海马炎症反应有关。 |
| 英文摘要: |
Objective To investigate the effects of minocycline pretreatment on the learning and memory impairment induced by isoflurane exposure in old mice.
Methods Fouty-eight healthy male SD rats, aged 20 months old, weighing 350-400 g, were randomly divided into three groups: normal sodium group (group NS),Iso group (group Iso), Minocycline pretreatment group (group M); 16 in each group. Group NS was control group, and rats in this group were injected same amount of normal sodium intraperitoneally. While in group Iso, the rats were exposed to 2.5% isoflurane for 3 min to induce anesthesia and then exposed to 1.5% isoflurane for 4 h to maintain anesthesia; while in group M, except minocycline was injected intraperitoneally (per 50 mg/kg) 30 min before isoflurane anesthesia,the rest treatment was the same as in group Iso. Cognitive tests including Morris water maze and Openfield test were carried out 24 h after the isoflurane anesthesia. Rats in each group were sacrificed immediately after the test, and hippocampi were harvested to determine the expression of inflammatory cytokines including IL-6,IL-1 and TNF-α using ELISA.
Results Compared with group NS, the escape latency of group Iso was significantly prolonged (P < 0.05) on the second, the third and the fourth days, the stay time in the platform quadrant was significantly shortened, the number of crossing platform quadrants decreased significantly on the fifth day (P < 0.05), and the retention time in the central area of the first, the second and the third day was significantly shortened (P < 0.05). Compared with the Iso group, the escape latency was significantly shortened in group M (P < 0.05) on the second, the third and the fourth days, on the fifth day platform quadrant time was obviously prolonged, the number of crossing platform quadrants increased significantly (P < 0.05), and the retention time in the central area on the first, the second and the third days was obviously prolonged (P < 0.05). Compared with group NS, the concentration of IL-1, IL-6 and TNF-alpha in the hippocampus of group Iso increased significantly (P < 0.05). Compared with group Iso, the concentration of IL-1, IL-6 and TNF-alpha in the hippocampus of group M decreased significantly (P < 0.05). There was no significant difference in the indexes between group NS and group M at different time points.
Conclusion Cognitive dysfunction induced by isoflurane exposure can be reversed by minocycline pretreatment in old rats, which may be associated with the down-regulation of the excessive release of hippocampal cytokines. |
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