Abstract：Objective: To explore the effects of esketamine (ESK) on depressive-like behaviors and activation of microglia in rats with depression by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. Methods: The rats with depression were constructed, and successfully modeled rats were separated into model group, L-ESK group, H-ESK group (intraperitoneal injection of 10 and 20mg/kg ESK), and ESK+RS09 group (intraperitoneal injection of 20mg/kg ESK+25μg/kg RS09), with 10 rats in each group. Another 10 normally fed rats were marked as the control group. The model group and control group were intraperitoneally injected with an equal amount of physiological saline, once a day for three consecutive weeks. After the administration, rats in each group was weighed, subjected to forced swimming test, sucrose preference test, and open field test. ELISA was used to measure the TNF-α, IL-6, and IL-10 in rat serum. HE staining was used to measure pathological changes in rat hippocampal tissue. Immunohistochemistry was applied to measure the Iba-1, CD206, and iNOS in hippocampal tissues. Moreover, Western blot was applied to detect the TLR4, MyD88, and NF-κB proteins in rat hippocampal tissues. Results: Compared with the control group, the arrangement of hippocampal neurons in the model group was disordered and loose, with phenomena such as vacuoles and nuclear degeneration and transformation observed. The levels of TNF-α, IL-6, Iba-1, iNOS, TLR4, MyD88, and NF-κB were elevated, while the body weight, sucrose preference, number of crawling steps, standing times, IL-10, and CD206 were decreased (P<0.05). Compared with the model group, the damage of hippocampal tissues in the L-ESK and H-ESK groups was alleviated successively. The levels of inactive time, TNF-α, IL-6, Iba-1, iNOS, TLR4, MyD88, and NF-κB were decreased, while the body weight, sucrose preference, number of crawling steps, standing times, IL-10, and CD206 were increased (P<0.05). Compared with the H-ESK group, the levels of inactive time, TNF-α, IL-6, Iba-1, iNOS, TLR4, MyD88, and NF-κB were increased in the ESK + RS09 group, while the body weight, sucrose preference, number of crawling steps, standing times, IL-10, and CD206 were decreased (P<0.05). Conclusion: ESK may inhibit the activation of microglia in rats with depression and improve depressive-like behaviors by suppressing the TLR4/MyD88/NF-κB pathway.
刘璇, 张晓敏, 刘进婷, 郝岩, 汪业铭, 陈红. 基于TLR4/MyD88/NF-κB通路探讨艾司氯胺酮对抑郁症大鼠抑郁样行为及小胶质细胞活化的影响[J]. 河北医学, 2026, 32(1): 13-19.
LIU Xuan, ZHANG Xiaomin, LIU Jinting, et al. The Effects of Esketamine on Depressive-Like Behaviour and Microglial Activation in Rats with Depression via the TLR4/MyD88/NF-κB Pathway. HeBei Med, 2026, 32(1): 13-19.
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2026, Vol. 32 
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