Effect of Duloxetine Combined with Olanzapine on Neuroinflammation and BDNF/TrkB Signaling Pathway in Rats with Chronic Stress Depression
WANG Li1, LIANG Junfeng2 *, BIAN Yuan2
This study aims to explore the effect of duloxetine combined with olanzapine on neuroinflammation in rats with chronic stress depression based on the BDNF/TrkB signaling pathway, and to investigate its possible mechanism of action. Sixty 6-week-old rats were randomly divided into the Con group (control group), Mod group (model group), Dul group (duloxetine group), Ola group (olanzapine group), Com group (duloxetine combined with olanzapine group), with 12 rats in each group. A chronic stress depression model was established by long-term stimulation of rats with random unpredictable stress behaviors. The open field test, sucrose preference test, and forced swimming test were used to detect behavioral changes in rats. HE staining was performed to observe morphological changes in hippocampal tissues. ELISA was used to detect the levels of 5-HT, DA, NE, IL-6, and TNF-α in rat hippocampal tissues. TUNEL staining was used to observe the apoptosis level of hippocampal neurons. Western blot was used to detect the levels of BDNF, TrkB, PI3K, p-AKT/AKT in hippocampal tissues. Compared with the Con group, the Mod group showed a significant decrease in total activity distance and sucrose preference rate (P<0.05), an prolongation in immobility time in the forced swimming test (P<0.05), aggravated pathological damage, decreased levels of 5-HT, DA, NE, and protein levels of BDNF and TrkB (P<0.05), and increased levels of IL-6, TNF-α, and neuronal apoptosis (P<0.05). Compared with the Mod group, the Dul group, Ola group, and Com group had a longer total activity distance and significantly higher sucrose preference rate (P<0.05), and a shorter immobility time in the forced swimming test (P<0.05), alleviated pathological damage, increased levels of 5-HT, DA, NE, BDNF, TrkB, PI3K, pAKT/AKT (P<0.05), and decreased levels of IL-6, TNF-α, and neuronal apoptosis (P<0.05). Compared with the Dul group and Ola group, the Com group had significantly increased total activity distance and sucrose preference rate (P<0.05), decreased immobility time in the forced swimming test (P<0.05), alleviated pathological damage, increased levels of 5-HT, DA, NE, BDNF, TrkB, PI3K, p-AKT/AKT (P<0.05), and decreased levels of IL-6, TNF-α, and neuronal apoptosis (P<0.05). Duloxetine combined with olanzapine has a therapeutic effect on rats with chronic stress depression, and its mechanism may be related to activating the BDNF/TrkB signaling pathway, increasing the content of monoamine neurotransmitters, and inhibiting neuroinflammation and cell apoptosis.
CN
EN