CB2-PKC通路参与了艾氯胺酮对暴露于脂多糖的BV-2小胶质细胞的抗炎作用。
The CB2-PKC pathway is involved in esketamine-induced anti-inflammation in BV-2 microglial cells exposed to lipopolysaccharides.
作者信息
Wang Yuqing, Cao Ming, Zhang Yuanyuan, Chen Qian, Chen Zhaojie, Jia Ji
机构信息
The Fourth Resident Outpatient Department, General Hospital of Southern Theatre Command of PLA Guangzhou 510501, Guangdong, China.
Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA Guangzhou 510501, Guangdong, China.
出版信息
Am J Transl Res. 2024 Sep 15;16(9):4466-4478. doi: 10.62347/RRZF5229. eCollection 2024.
OBJECTIVE
Esketamine (ESK), an intravenous anesthetic, exerts antidepressant effects; however, the antidepression mechanism is not clear. The aim of this study was to explore whether microglial cannabinoid type 2 (CB2) receptor and protein kinase C (PKC) are involved in the antidepressant effects of ESK.
METHODS
In this investigation, lipopolysaccharide (LPS) was used to stimulate BV-2 microglia to mimic neuroinflammation. An enzyme-linked immunosorbent assay (ELISA) and Griess reagent kits were used to determine cytokine and nitrite concentrations in the medium. CB2, inducible nitric oxide synthase (iNOS) and nuclear factor (NF)-κB (p65) protein expression were evaluated by immunocytochemistry and western blot analysis.
RESULTS
Compared with the control, LPS enhanced proinflammatory factor and nitrite concentration in the medium, upregulated iNOS and NF-κB (p65) expressions, and coadministration of ESK decreased proinflammatory cytokine and nitrite levels, and downregulated iNOS and NF-κB (p65) expression. Moreover, ESK exposure enhanced CB2 receptor expression; coadministration of the CB2 receptor antagonist AM630 or the PKC inhibitor chelerythrine (Che), however, markedly blocked the anti-inflammatory effect of ESK in reducing cytokine and nitrite concentration, and downregulating iNOS and NF-κB (p65) expression.
CONCLUSIONS
These observations demonstrated that the microglial CB2-PKC pathway mediates ESK-induced anti-inflammation in LPS-stimulated microglial cells.
目的
艾司氯胺酮（ESK）作为一种静脉麻醉剂，具有抗抑郁作用；然而，其抗抑郁机制尚不清楚。本研究旨在探讨小胶质细胞2型大麻素（CB2）受体和蛋白激酶C（PKC）是否参与了ESK的抗抑郁作用。
方法
在本研究中，使用脂多糖（LPS）刺激BV-2小胶质细胞以模拟神经炎症。采用酶联免疫吸附测定（ELISA）和格里斯试剂试剂盒测定培养基中的细胞因子和亚硝酸盐浓度。通过免疫细胞化学和蛋白质印迹分析评估CB2、诱导型一氧化氮合酶（iNOS）和核因子（NF）-κB（p65）蛋白表达。
结果
与对照组相比，LPS增加了培养基中促炎因子和亚硝酸盐浓度，上调了iNOS和NF-κB（p65）表达，而ESK共同给药降低了促炎细胞因子和亚硝酸盐水平，并下调了iNOS和NF-κB（p65）表达。此外，ESK暴露增强了CB2受体表达；然而，CB2受体拮抗剂AM630或PKC抑制剂白屈菜红碱（Che）共同给药显著阻断了ESK在降低细胞因子和亚硝酸盐浓度以及下调iNOS和NF-κB（p65）表达方面的抗炎作用。
结论
这些观察结果表明，小胶质细胞CB2-PKC途径介导了ESK在LPS刺激的小胶质细胞中诱导的抗炎作用。
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