| 覃斌，叶刚，吴述轩，向登国，牟俊英，朱贤林.氯胺酮通过抑制ERK1/2/NF-κB信号通路发挥抗抑郁作用[J].神经损伤功能重建,2020,15(3):134-137 |
| 氯胺酮通过抑制ERK1/2/NF-κB信号通路发挥抗抑郁作用 |
| Inflammation-Related Mechanism of Ketamine Exerting Antidepressant Effect by InhibitingERK1/2/NF-κ B Signaling Pathway |
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| DOI： |
| 中文关键词: 氯胺酮 ERK1/2/NF-κB信号通路 炎症反应 |
| 英文关键词: ketamine ERK1/2/NF-κB signaling pathway inflammatory response |
| 基金项目:湖北省自然科学基
金面上项目（No.20
16CFB368）；
国家自然科学基金
（No.81760257） |
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| 中文摘要: |
| 目的：探讨氯胺酮通过抑制ERK1/2/NF-κB信号通路发挥抗抑郁作用的炎症相关机制。方法：15只正
常大鼠为空白对照组（Blank组），慢性不可预知刺激抑郁模型法构建成功的45只抑郁大鼠随机分为对照组
（Con组）、安慰剂组（Place组）、实验组（Exp 组）3组，每组15只。Con组不予药物，Place组建模成功后给予
安慰剂灌胃，Exp组给予氯胺酮灌胃21 d。治疗前后，采用悬尾实验、强迫游泳实验、新奇抑制摄食实验检测
行为学改变；ELISA、qRT-PCR检测海马组织白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子-α（TNF-α）各组表
达；Western blot检测海马组织ERK1/2、NF-κB炎症相关信号分子改变。结果：在行为学实验中，氯胺酮能显
著缩短抑郁大鼠游泳不动时间（P<0.05）及悬尾不动时间（P<0.01）。无论在蛋白水平还是mRNA水平，Con
组IL-1β、IL-6、TNF-α表达高于Blank组（P<0.05）；Exp组的IL-1β、IL-6、TNF-α表达较Con组下降（P＜0.05）。
Con组的pERK1/2、pNF-κB蛋白表达高于Blank组，Exp组的pERK1/2、pNF-κB蛋白表达较Con组下降（P＜ 0.05）。结论：氯胺酮通过抑制ERK1/2、NF-κB信号分子，抑制炎症反应，显著改善抑郁大鼠的行为学。 |
| 英文摘要: |
| To investigate the inflammation-related mechanisms through which ketamine exerts antidepressant effects by inhibiting the ERK1/2/NF-κB signaling pathway. Methods: Fifteen normal rats were assigned to the blank control group (Group Blank). Chronic unpredictable stimulation was used to generate the depression rat model, and 45 successfully constructed depressed rats were randomly divided into three groups: control group (Group Con), placebo group (Group Place), and experimental group (Group Exp), with 15 rats in each
group. Group Con was not given medication; Group Place was given placebo by oral gavage after successful
model establishment; Group Exp was given ketamine by oral gavage for 21 days. Behavioral changes were detected by tail suspension test, forced swimming test, and novelty inhibition feeding test before and after treatment. The expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in the hippocampus
was detected by ELISA and qRT-PCR. Changes in signal molecules related to ERK1/2 and NF-κB inflammation
in the hippocampus were detected by Western blotting. Results: Ketamine significantly shortened swimming immobility time (P<0.05) and tail suspension immobility time (P<0.01) in behavioral experiments. The expression
of IL-1β, IL-6, and TNF-α in Group Con was significantly higher than that in Group Blank at both protein and
mRNA levels. In addition, the expression of IL-1β, IL-6, and TNF-α in Group Exp was significantly lower than
that in Group Con (P<0.05). The expression of pERK1/2 and pNF-κB in Group Con group was significantly higher than that in Group Blank, while the expression of pERK1/2 and pNF-κB in Group Exp group were significantly lower than that in Group Con (P<0.05). Conclusion: Ketamine can significantly improve the behavior of depressed rats by inhibiting inflammation through inhibiting signal molecules of ERK1/2 and NF-kB. |
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