Study On The Mechanism Of Inflammatory Reaction In Depression After Acute Myocardial Infarction In Rats

Patients with acute myocardial infarction have a high risk of all kinds of complications,depression is one of the common one. On the one hand,the incidence ofpost-MI patients with depressive disorders is much higher than the prevalence in the general population.Patients with depressive symptoms,on the other hand,also increased the risk of cardiovascular disease. The coexistence of these two situations lead to a poor prognosis for the patients.In recent years,the depression in patients with acute coronary events,especially the so-called depression after myocardial infarction is considered to be an independent risk factor for the prognosis of coronary heart disease, which has attracted more and more attention of cardiovascular clinicians.The function of the heart founded on the Modern medicine which based on the anatomical although not be equivalent to the concept of heart as with traditional Chinese medicine,the occurrence of depression after myocardial infarction make people realize that there is a certain link in the pathology between heart and brain.Consciousness activity is originated in the heart and then reaches to the brain,there is a close correlation between the heart and brain.The interaction mechanism of myocardial infarction and depression is still unclear.The inflammation has been shown to have a relationship with both myocardial infarction and depress ion, however, the mechanism of depression after myocardial infarction whether associated with the inflammation has not been determined. There fore, we collected the data from the laboratory to clarify the mechanism of the inflammation in depression after acute myocardial infarction.The purpose of the study:To observe the changes of neural behavior in rats after myocardial infarction,to detect the pro inflammatory cytokines concentrations of AMI rats in circulating blood and hippocampus of the limbic system,to research the correlation between the changes of neural behavior and the expression of the pro inflammatory cytokines in rats after myocardial infarction,to determine whether the depressive symptoms after myocardial infarction in rats improvements can be improved by pro-inflammatory cytokine inhibitor-pentoxifylline,In order to reveal the mechanism of depression after myocardial infarction.The significance of the study:To reveal the relationship between the heart and the mind from the pathogenesis of depression after myocardial infarction,and to provide new targets for clinical therapeutic effect on depression after myocardial infarction.The methods of the study:1.Animal Grouping and molding:100 adult healthy male Wister rats,weighing 180-200g,SPF grade,three days to adapt the environment,then research the behavioral score, select the similar score rats and then randomly divided.(1)Moldle group:The rats were given thoracotomy and left front descending coronary artery ligation;(2)PTX group:the same to the modle group,0.2ml/100g PTX was given for 7days after operation;(3)Sham-operated group: the same to the modle group,received thoracotomy but without ligatioa2.Observation Indexes:2.1 ECG:To observe the ECG of each group.2.2 Ethology experiments:Sucrose water consumption test,performed 7days before and after the operation;Open field test、Forced swimming test and Morris water maze test were performed 14days after operation.2.3 The pathological changes in myocardial tissue were tested by HE staining.2.4 To detect the concentration of pro-inflammatory cytokine TNF-α、IL-1β、IL-6 in circulating blood and hippocampus of the limbic system each group.The result of the study:1.ECG:The ECG of the sham group have little change after surgery,while the model group rats showed standard II in ST segment is arch upward and lasts 30 min.2.Ethology experiments:2.1 Sucrose water consumption test Compared with the sham group,the consumption of sucrose of model group were significantly decreased(P<0.05);Compared with the model group,the consumption of sucrose of PTX group were significantly increased(P<0.05).2.2 Open field test:Compared with the sham group,the score of horizontal movement and vertical movement of model group were significantly decreased(P<0.05);Compared with the model group,the score of horizontal movement and vertical movement of PTX group were significantly increased(P<0.05).2.3 Forced swimming test:Compared with the sham group,the immobility time of model group was significantly increased(P<0.05);Compared with the model group,the immobility time of PTX group was significantly reduced(P<0.05).2.4 Morris water maze test:The escape latency of each group has no significant difference between the first three days of the experiment(P>0.05).On the fourth day of the experiment,Compared with the sham group,the escape latency of model group was significantly increased(P<0.05);Compared with the model group,the escape latency of PTX group was significantly reduced(P<0.05).After dropping the platform,Compared with the sham group, the number of crossing the original platform and the target quadrant dwell time of the model group decreased significantly(P<0.05);Compared with the model group,the number of crossing the platform and the target quadrant dwell time of the PTX group increased significantly(P<0.05).3.The results of HE staining showed that the order of myocardial fiber was normal in the sham group,But myocardial fiber disorder, myofilament fracture,nuclear pyknosis,karyolysis and fraction of myocardial cells,a large number of inflammatory cell infiltration and visible granulation tissue hyperplasia were observed in the model group.The alterations in the PTX group was less serious than the model group.4.The concentration of pro-inflammatory cytokine TNF-α、IL-β、IL-6 in circulating blood:Compared with the sham group,the concentration of TNF-αand IL-1βin circulating blood of model group was significantly increased (P<0.05),the concentration of IL-6 in circulating blood increased but no significant difference (P>0.05);Compared with the model group,the concentration of TNF-α and IL-1β in circulating blood of PTX group was significantly decreased(P<0.05),the concentration of IL-6 in circulating blood decreased but no significant difference(P>0.05).5.The concentration of pro-inflammatory cytokine TNF-α、IL-1β、IL-6 in hippocampus of the limbic system:Compared with the sham group,the concentration of TNF-α、IL-β in the hippocampus of the limbic system of model group was significantly increased(P<0.05), the concentration of IL-6 increased but no significant difference(P>0.05);Compared with the model group, the concentration of TNF-α、IL-1β in hippocampus of the limibic system of PTX group was significantly decreased(P<0.05),the concentration of IL-6 decreased but there was no siginificant differerce(P>0.05).The conclusion of the study:1.The rats after acute myocardial infarction showed typical symptoms of depression were similar to human beings:lack of pleasure,low mood,lack of interest,exercise and exploring disability.2. The inflammation factors significantly increased in circulating blood and hippocampus of the limbic system suggested nerve inflammation appeard.3.After using the inflammatory cytokine blockers-PTX,inflammation were suppressed, and at the same time,the depressive symptoms of the AMI rats are also improved.4.The inflammatory mechanism of post-AMI depression provided the biological basis for heart Governing Mind Theory of traditional Chinese medicine.