OBJECTIVE To investigate the pharmacodynamics and related mechanisms of Anmei Dan on hippocampus of mice with coronary heart disease complicated with depression.

METHODS The coronary heart disease model combined with chronic and unpredictable mild stress depression model was established, and the mice were randomly divided into blank group, model group, low dose group (1.5 g ·kg^-1), high dose group (3 g ·kg^-1) and atorvastatin group (0.3 g ·kg^-1). Sucrose preference test, open field test and forced swimming test were used to evaluate the behavioral changes of mice. qPCR and ELISA were employed to ascertain the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in the hippocampus. The changes of neurons and Nissl bodies in CA1, CA3 and DG regions of hippocampus were observed by Nissl staining. The expression of key proteins was detected by Western blot.

RESULTS Compared with the blank group, the sucrose preference rate of mice in the model group was decreased (P < 0.01), the forced swimming immobility time was extended (P < 0.01) and the movement distance in the open field experiment was not significantly changed. The levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) were increased significantly (P < 0.01) and the level of high density lipoprotein cholesterol (HDL-C) was decreased significantly (P < 0.01). The mRNA level and content of IL-1β, IL-6 and TNF-α were significantly increased (P < 0.01). The expression of glutamate receptor 1 (GluR1), postsynaptic densitin-95 (PSD-95), brain-derived neurotrophic factor (BDNF) and phosphorylated calmodulin-dependent kinase (p-CaMKⅡ) in hippocampus was decreased (P < 0.01). The expression of cytoskeletal activity regulatory protein (Arc) was increased (P < 0.01). In the model group, the cell structure was irregular and different degrees of damage occurred, the Nissl bodies decreased or disappeared, and the cell membrane broke. Compared with the model group, the sucrose preference rate of mice in each administration group was significantly increased (P < 0.01), the immobility time in forced swimming experiment was significantly decreased (P < 0.01), and the levels of TC, TG and LDL-C of mice in Anmei Dan groups and atorvastatin group were decreased (P < 0.01), while the level of HDL-C increased (P < 0.01). The mRNA levels and content of IL-1β, IL-6 and TNF-α in Anmei Dan groups and atorvastatin group were decreased (P < 0.01). The expression of GluR1, PSD-95, BDNF and p-CaMKⅡ in hippocampal tissue of Anmei Dan groups were increased (P < 0.01), and the expression of Arc was decreased (P < 0.01). The morphology and structure of the cells in the Anmei Dan group and the atorvastatin group were improved, with varying degrees of increased Nissl bodies and relatively intact cell membranes.

CONCLUSION Anmei Dan can effectively improve blood lipids and depression-like behavior of coronary heart disease mice complicated with depression. It can inhibit pro-inflammatory factors, increase the expression of neurotrophic factors, effectively improve synaptic related proteins, and reduce the damage to neurons, thus effectively preventing the exacerbation of coronary heart disease and depression comorbidity.