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Article in Chinese | WPRIM | ID: wpr-940832


ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity (COM) model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group (Chow), a diet-induced obesity group (DIO), and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group, a COM group, and a tumor necrosis factor-α(TNF-α) knock-down group. In the TNF-α knock-down group, TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis, and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group, a DIO group, a DIO + low-dose tripterine group (0.5 mg·kg-1), a DIO + high-dose tripterine group (1.0 mg·kg-1), a COM group, a COM + low-dose tripterine group (0.5 mg·kg-1), and a COM + high-dose tripterine group (1.0 mg·kg-1). The body weight, food intake, glucose tolerance, white/brown fat ratio, serum total cholesterol (TC), triglyceride (TG), and high-/low-density lipoprotein cholesterol (HDL-C and LDL-C) content were recorded, and obesity of mice in each group was evaluated. Forced swimming test (FST), tail suspension test (TST), and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y, tryptophan hydroxylase 2 (TPH2), and brain-derived neurotrophic factor (BDNF) in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific, obesity was manifested as increased body weight and food intake (P<0.05, P<0.01), as well as increased NPY expression in the central amygdala, and depression was manifested as prolonged immobility time in FST and TST (P<0.01), and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus (DRN) and basolateral nucleus of the amygdala (BLA). The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST (P<0.05, P<0.01), increased TPH2/BDNF-positive neurons in BLA, and showed no significant changes in obesity. In DIO mice, the administration of 0.5 mg·kg-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance (P<0.01) and food intake (P<0.05). In COM mice, 1.0 mg·kg-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance (P<0.01), and food intake (P<0.05), and immobility time in TST (P<0.01), increase TPH2-BDNF double-labeled cells in BLA and DRN, and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity, and its mechanism may be related to the inhibition of central nervous system inflammation.