Study on the Mechanism of Tanshinone ⅡA against Coronary Heart Disease with Comorbid Depression in ApoE^-/- Mice

  OBJECTIVE  To investigate the effect and mechanism of tanshinone ⅡA against coronary heart disease with comorbid depression in ApoE^-/- mice.

  METHODS  The model of coronary heart disease with comorbid depression was established by feeding high fat diet and carrying out chronic unpredictable mild stress (CUMS). Mice were randomly divided into normal group, model group, tanshinone ⅡA low dose group (30 mg · kg^-1) and tanshinone ⅡA high dose group (60 mg · kg^-1). Hematoxylin-eosin (HE) and oil red O staining were used to detect the pathological changes of cardiac aortic sinus in ApoE^-/- mice. Forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to observe the depression-like behaviors of ApoE^-/- mice. The levels of blood lipid and inflammatory factors were detected by ELISA assay. The expressions of inflammation related proteins in cardiac aortic sinus and hippocampus were detected by Western blot.

  RESULTS  Compared with the normal group, the lipid accumulation in the cardiac aortic intima in the model group increased significantly, the levels of blood lipid and pro-inflammatory factors increased significantly (P < 0.01), the immobility time of FST and TST significantly increased (P < 0.01), while the sucrose preference rate of SPT significantly decreased (P < 0.01), the ratios of p-GSK3β (Ser9)/GSK3β, p-NF-κB/NF-κB and p-CREB (Ser133)/CREB in cardiac aortic sinus and hippocampus increased significantly (P < 0.01). Compared with the model group, the treatment with tanshinone ⅡA significantly reduced the accumulation of lipid in cardiac aortic intima, the levels of blood lipid and pro-inflammatory factors and the immobility time of FST and TST decreased significantly (P < 0.01), the sucrose preference rate of SPT significantly increased (P < 0.01), the ratio of p-NF-κB/NF-κB decreased significantly (P < 0.01), and the ratios of p-GSK3β(Ser9)/GSK3β and p-CREB(Ser133)/CREB increased significantly (P < 0.05, P < 0.01).

  CONCLUSION  Tanshinone ⅡA has a significant effect against coronary heart disease with comorbid depression in ApoE^-/- mice, and its mechanism may be related to the regulation of GSK3β, and further activation of NF-κB and CREB.