Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, Harbin 150030, China.
Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, Harbin 150030, China.
Int Immunopharmacol. 2019 Oct;75:105788. doi: 10.1016/j.intimp.2019.105788. Epub 2019 Aug 1.
Depression has become a common mental illness, and studies have shown that neuroinflammation is associated with depression. Ketamine is a rapid antidepressant. In order to obtain better antidepressant effects, it is necessary to explore the efficacy of combination therapy with ketamine and other antidepressants. DHA is an unsaturated fatty acid with excellent application prospects due to its safety and antidepressant effects. This study was designed to investigate the effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior. In behavioral experiments, lipopolysaccharide prolongs the immobility time of the forced swimming and tail suspension tests in rats and reduces the sucrose preference. The combination of ketamine and DHA can reverse these changes and work better than the single application. Nissl staining showed that ketamine combined with DHA can reverse the nerve damage caused by lipopolysaccharide. Cell morphology observation the combination of ketamine and DHA group was more complete than that of LPS group. The combination of ketamine and DHA significantly decreased the levels of IL-1, IL-6 and TNF-ɑin hippocampus and PC12 cells and increased the content of BDNF. Immunofluorescence results showed that ketamine combined with DHA can effectively inhibit PP65 nuclear translocation. Western blot results showed that ketamine combined with DHA can effectively inhibit the expression of NF-KB in hippocampus and PC12 cells, and increase the expression of P-CREB and BDNF. In summary, the combination of ketamine with DHA may be a more effective treatment for depression caused by inflammation and is mediated by inhibition of the inflammatory pathway.
抑郁症已成为常见的精神疾病，研究表明神经炎症与抑郁症有关。氯胺酮是一种快速抗抑郁药。为了获得更好的抗抑郁效果，有必要探索氯胺酮与其他抗抑郁药联合治疗的疗效。二十二碳六烯酸（DHA）是一种不饱和脂肪酸，由于其安全性和抗抑郁作用，具有广阔的应用前景。本研究旨在探讨氯胺酮联合 DHA 对脂多糖诱导的抑郁样行为的影响。在行为实验中，脂多糖延长了大鼠强迫游泳和悬尾试验中的不动时间，降低了蔗糖偏好。氯胺酮和 DHA 的联合应用可以逆转这些变化，且效果优于单一应用。尼氏染色显示，氯胺酮联合 DHA 可以逆转脂多糖引起的神经损伤。细胞形态观察显示，氯胺酮联合 DHA 组比 LPS 组更完整。氯胺酮联合 DHA 显著降低了海马和 PC12 细胞中 IL-1、IL-6 和 TNF-ɑ的水平，并增加了 BDNF 的含量。免疫荧光结果显示，氯胺酮联合 DHA 能有效抑制 PP65 核转位。Western blot 结果显示，氯胺酮联合 DHA 能有效抑制海马和 PC12 细胞中 NF-KB 的表达，增加 P-CREB 和 BDNF 的表达。综上所述，氯胺酮与 DHA 的联合应用可能是一种更有效的炎症相关抑郁症治疗方法，其作用机制可能是通过抑制炎症通路。
