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| 氯离子转运蛋白NKCC1在老年小鼠术后认知功能障碍中的作用 |
| Role of chloride transporter NKCC1 in postoperative cognitive dysfunction in aged mice |
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| DOI：10.12089/jca.2022.09.015 |
| 中文关键词: 氯离子转运蛋白 钠离子钾离子氯共转运体1 术后认知功能障碍 老年 |
| 英文关键词: Chloride transporter NKCC1 Postoperative cognitive dysfunction Aged |
| 基金项目:国家自然科学基金（81772126，81971892） |
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| 中文摘要: |
目的 探讨氯离子转运蛋白钠离子钾离子氯共转运体1（NKCCl）在老年小鼠术后认知功能障碍（POCD）中的作用。
方法 选择老年雄性C57BL/6小鼠40只，18～20月龄，体重28～32 g。将小鼠随机分为四组：对照+生理盐水组（N组），对照+布美他尼（NKCC1抑制剂）组（B组），POCD模型+生理盐水组（M组）和POCD模型+布美他尼组（MB组），每组10只。采用异氟醚麻醉和剖腹探查术建立POCD动物模型，于术后3～7 d行旷场与条件恐惧实验评估认知功能；行为学结束后采用Western blot法检测海马组织NKCC1、钾离子氯离子共转运体2（KCC2）、脑源性神经营养因子（BDNF）及突触后密度蛋白95（PSD95）的蛋白含量，免疫组织荧光检测海马组织CA1、CA3、DG区NKCC1免疫荧光强度。
结果 与N组比较，M组场景僵直时间明显缩短（P<0.05），海马NKCC1蛋白含量明显升高（P<0.05），BDNF、PSD95蛋白含量明显降低（P<0.05），海马组织CA1、CA3、DG区NKCC1免疫荧光强度明显增强（P<0.05）。N组和B组各指标差异均无统计学意义。与M组比较，MB组场景僵直时间明显延长（P<0.05），海马NKCC1蛋白含量明显降低（P<0.05），BDNF、PSD95蛋白含量明显升高（P<0.05），海马组织CA1、CA3、DG区NKCC1免疫荧光强度明显减弱（P<0.05）。
结论 NKCC1可能在老年小鼠POCD中发挥关键作用，其机制可能与突触相关蛋白BDNF与PSD95表达水平下调有关。 |
| 英文摘要: |
Objective To explore the role of chloride transporter NKCC1 in postoperative cognitive dysfunction (POCD) in elderly mice.
Methods Forty male C57BL/6 mice, aged 18-20 months, weighing 28-32 g, were used to establish POCD animal model by isoflurane anesthesia and exploratory laparotomy. Mice were randomly divided into four groups: control + normal saline group (group N), control + bumetanide (NKCC1 antagonist) group (group B), POCD model + saline group (group M) and POCD model + bumetanide group (group MB), 10 mice in each group. The POCD model was assessed by open field test and fear conditioning test on 3-7 days after operation. Western blot was used to evaluate the protein content of hippocampal NKCC1, potassium-chloride cotransporter-2 (KCC2), brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95). The expression of NKCC1 in hippocampus was detected by immunofluorescence.
Results Compared with group N, the freezing time was significantly shortened in group M (P < 0.05), the expression of NKCC1 in hippocampus was significantly increased while the expressions of BDNF and PSD95 were decreased significantly in group M (P < 0.05), the immunofluorescence intensity of NKCC1 in CA1, CA3 and DG areas of hippocampus were significantly increased in group M (P < 0.05). There were no significantly differences in the above indexes between the two groups. Compared with group M, the freezing time was significantly prolonged in group MB (P < 0.05), the expressions of NKCC1 was significantly decreased while BDNF and PSD95 increased significantly in group MB (P < 0.05), the immunofluorescence intensity of NKCC1 in CA1, CA3 and DG areas of hippocampus were significantly decreased in group MB (P < 0.05).
Conclusion NKCC1 might play a key role in POCD in elderly mice, which may be related to the decreased synaptic associated protein BDNF and PSD95. |
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