The effect of Wendan Ningxin granules on the BDNF/TrkB/PI3K/Akt signaling pathway in rats with myocardial infarction and depression
Objective:This study observed the effect of Wendan Ningxin Granules(WDNX)on the BDNF/TrkB/PI3K/Akt signaling pathway in rats with myocardial infarction and depression,and explored its possible mechanism of action.Methods:A rat model of myocardial infarction combined with depression was prepared by subcutaneous multi-point injection of isoproterenol(ISO)and chronic unpredictable mild stress(CUMS).After 28 days of intervention with WDNX,changes in cardiac function were detected by transthoracic echocardiography;Evaluate the depression status of rats based on sugar preference and open field experiments;Using hematoxylin eosin(HE)and Nissl staining to observe pathological changes in myocardial and brain tissue,as well as neuronal damage;Finally,the expression levels of the BDNF/TrkB/PI3K/Akt pathway were detected using immunohis-tochemistry and Western blotting techniques.Results:In vivo experiments have confirmed that compared with the blank group,the left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(LVFS)of the model group rats were significantly reduced(P<0.01).A large amount of fiber edema and cytoplasmic looseness were observed in the myocardial tissue,and myocardial fiber dissolution was observed at the tissue edge,accompanied by a small amount of lymphocyte infiltration;There is obvious diffuse damage to brain tissue,interstitial swelling,aggregation of inflammatory cells,and irregular morphology;Nissl staining observation showed that the number of neurons in the model group significantly decreased,with irregular morphology,loose and disordered arrangement,increased intercellular spaces,and also led to the consolidation of Nissl body morphology,re-sulting in pathological changes;The preference for sugar water,activity time in the central region,and number of central crossings in the model rats were significantly reduced(P<0.01);Compared with the model group,the WDNX group showed a significant increase in LVEF and LVFS(P<0.01),with improvements in myocardial fiber edema,cytoplasmic looseness,inflammatory in-filtration,cell cavity degeneration,and fiber dissolution.The morphology of neurons in the brain tissue was more regular,ar-ranged neatly and tightly,and the number of neurons was relatively increased.It was also possible to restore the morphology of Nissl bodies;The preference for sugar water,activity time in the central region,and number of central crossings in the WDNX group of rats significantly increased(P<0.05).Immunohistochemical staining results:Compared with the blank group,the BDNF protein expression in the myocardial and brain tissues(hippocampus,cortex,and hypothalamus)of the model group rats was significantly reduced(P<0.01),while the expression of TrkB,PI3K,and Akt proteins in the myocardium was significantly reduced(P<0.01);Compared with the model group,the expression of BDNF protein in the myocardium and brain tissues(hip-pocampus,cortex,and hypothalamus)of the WDNX group was significantly increased(P<0.05),while the expression of TrkB,PI3K,and Akt proteins in the myocardium were significantly increased(P<0.01);Western blotting test results:Compared with the blank group,the expression of BDNF,TrkB,PI3K,and Akt proteins in the myocardium of the model group rats was signifi-cantly reduced(P<0.01);Compared with the model group,the expression of BDNF,TrkB,PI3K,and Akt proteins in the myo-cardium of the WDNX group was significantly increased(P<0.05).Conclusion:WDNX can effectively improve myocardial inju-ry and depressive behavior in rats with myocardial infarction and depression,which may be related to the activation of the BDNF/TrkB/PI3K/Akt pathway.
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