关键词: 青蒿琥酯, 环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子通路, 抑郁症, 炎性反应, 凋亡

Abstract: Objective To investigate the effect of artesunate (ART) on neuroinflammation in depressed mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway. Methods Mice were divided into model group, control group, low-dose ART group, high-dose ART group, fluoxetine group, and high-dose ART+RocA (cGAS-STING pathway activator) group. Sugar solution consumption experiment and forced swimming experiment were applied to evaluate the depressive behavior of mice; HE staining microscopy was applied to detect pathological changes in hippocampal tissue; ELISA method was applied to detect the level of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), serotonin(5-HT) and dopamine (DA); TUNEL staining microscopy was applied to detect neuronal apoptosis; Western blot was applied to detect Bcl-2 associated X protein (Bax), p53, cGAS, and STING proteins. Results Compared to the control group, the mice in the model group exhibited neuronal pustule degeneration, the sugar water consumption rate, level of 5-HT and DA decreased, the rest time of forced swimming increased. The level of IL-6 and TNF-α, neuronal apoptosis rate, expression of Bax, p53, cGAS, and STING proteins all elevated (P＜0.05); Compared with model group, the damage to hippocampus neurons in the ART low-dose group, ART high-dose group and fluoxetine group neuronal pustular degeneration was alleviated, while sugar water consumption rate, 5-HT, and DA levels increased, the rest time of forced swimming reduced, the level of IL-6 and TNF-α, neuronal apoptosis rate and the expression of Bax, p53, cGAS, and STING proteins reduced (P＜0.05); RocA reversed the improvement effect of high-dose ART on depression in mice. Conclusions ART inhibits neuroinflammation and neuronal apoptosis in depressed mice, and up-regulates amine neurotransmitters expression. The mechanism is potentially related to the blocking of cGAS-STING pathway.

Key words: artesunate, cyclic guanosine monophosphate-adenosine monophosphate synthase- stimulator of interferon gene pathway, depression, inflammation, apoptosis