| ObjectiveDepression and myocardial infarction are two major causes of death and disability worldwide.Depression is an independent risk factor for cardiovascular mortality and morbidity,and it is highly prevalent in myocardial infarction patients.Post-MI depression is a critical clinical problem,the comorbidity of which complicates depression treatment and worsens cardiovascular outcomes.To investigate the role of mitochondrial aldehyde dehydrogenase activator Alda-1 in reducing depression-like behavior in chronic unpredictable mild stress model rats,and to improve the prognosis of coronary heart disease and related mechanisms.Provide theoretical basis for clinical treatment of depression after myocardial infarction.MethodsFifty adult male SD rats were randomly divided into five groups:normal control group,myocardial infarction group,depression group,post-myocardial infarction depression group and Alda-1 group.The model was assessed by weight measurement,sugar preference test,forced swimming test,and multi-function closed labyrinth test,and the effect of Alda-1 on the behavioral changes of post-MI depression rats was examined.Immunohistochemistry was used to detect the expression of VEGF and CD34 in the hippocampus of rats.Western Blot was used to detect the expression of p-JNK/JNK and HIF-1/VEGF protein in hippocampus of rats.The levels of neurotransmitters in serum and hippocampus 5-HT and DA were measured by ELISA.Results1.Compared with the control group,the weight gain of depression group and post-myocardial infarction depression group decreased significantly(P<0.001),and the weight gain of Alda-1 group was significantly higher than that of post-myocardial infarction depression group(P<0.001);2.Compared with the control group,the sucrose consumption and the sucrose preference ratio of the depression group(p<0.05)and the depression group(p<0.001)decreased significantly,and the consumption of pure water increased significantly.Compared with the depression group after myocardial infarction,the sugar consumption(p<0.001)and sucrose preference ratio(p<0.01)of Alda-1 group increased significantly,while the consumption of pure water decreased significantly(p<0.01);3.Compared with the control group,the immobility time of depression group and post-myocardial infarction depression group was increased significantly(P<0.001),swimming latency decreased significantly(P<0.001).Compared with post-myocardial infarction depression group,the immobility time was shortened significantly(P<0.001)and swimming latency increased significantly(P<0.001)in the Alda-1 group;4.Compared with the control group,the labyrinth movement distance of depression group and post-myocardial infarction depression group decreased significantly(P<0.001),and the activity decreased significantly(P<0.001).Compared with the post-myocardial infarction depression group,the distance of movement increased significantly(P<0.001)and the activity increased significantly(P<0.001)in the Alda-1 group;5.The mean optical density of VEGF and CD34 in depression group and post-myocardial infarction depression group decreased significantly(P<0.001),MVD significantly decreased(P<0.05,p<0.001).Compared with post-myocardial infarction depression group,the mean optical density of VEGF and CD34 were significantly increased in Alda-1 group(P<0.001,p<0.01),MVD increased significantly(P<0.01);6.Compared with the control group,the expression of HIF-a(P<0,001)and VEGF(p<0.01,p<0.001)were significantly decreased in depression group and post-myocardial infarction depression group,the expression of p-JNK/JNK increased significantly.Compared with the depression group after myocardial infarction,the expression of HIF-a and VEGF(p<0.01)were significantly increased in the Alda-1 group,the expression of P-JNK/JNK decreased significantly(P<0.01);7.Compared with the control group,the expression levels of 5-HT(p<0.05,p<0.01)and DA(p<0.05,p<0.001)in serum in depression group and post-myocardial infarction depression group were decreased significantly,the expression levels of 5-HT(p<0.001,p<0.001)and DA(p<0.01,P<0.001)in hippocampus were significantly decreased.Compared with the post-myocardial infarction depression group,the expression of 5-HT and DA(p<0.05)in the serum of rats in the Alda-1 group was increased significantly,the expression of 5-HT(p<0.001)and DA(p<0.05)was significantly increased in the hippocampus.Conclusions1.The sugar preference test,forced-swimming test,and multi-function closed maze test showed that Alda-1 improved the depression-like behavior of depression rats after myocardial infarction.2.Alda-1 upregulated the expression of VEGF in hippocampus and increased the of hippocampal microvessel density.The specific mechanism is to directly promote hippocampal expression of VEGF by down-regulating p-JNK/JNK and up-regulating HIF-1 pathway.In addition,Alda-1 also promotes the expression of 5-HT and DA neurotransmitters in serum and hippocampus,thereby indirectly promoting expression of VEGF in the hippocampus.3.In summary,Alda-1 upregulated the expression of vegf in hippocampus,which improved the depressive behavior of post-myocardial infarction depression rats,and provided a new idea for the treatment of post-myocardial infarction depression. |
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