| Depression and coronary heart disease are common diseases that affect the whole world.With the gradual transformation of the medical model to the "bio-psychology-society" model,the influence of mental and psychological diseases on physical diseases has attracted more and more attention from the medical community.Depression is a common mental illness.According to statistics,globally,the lifetime risk of depression is about 3-16.9%,and there is no obvious age trend.Coronary heart disease is common in people over 40 years old,but in recent years,clinical findings of coronary heart disease show a younger age trend.For example,the American Heart Association(AHA)guidelines,released in 2015,clearly showed that severe depression and bipolar disorder can accelerate atherosclerosis and trigger early cardiovascular disease in young adults.Many evidences show that depression is an independent risk factor of cardiovascular disease,and that depression interacts with heart disease through the autonomic nervous system and other mechanisms,aggravating the disease and seriously affecting the quality of life of patients worldwide:Therefore,it is necessary to study the prevention and treatment of depression-related heart disease.In clinical practice,we found that the guizhi decoction can alleviate symptoms of depression in patients with heart,such as insomnia,palpitation,chest tightness,chest pain,and running of the dolphin,cassia twig decoction is a representative of the clinical commonly used method of harmonic camp guard prescriptions,therefore,who speculated to reconcile camp treatment may have to adjust mood,protect the heart of the action,but the mechanism is unknown.For the system in this paper,the harmonic camp guard for heart protection mechanism of the curative effect of depression,this topic proposed by chronic unpredictable mild stress(chronic unpredictable mild stess,CUMS)method to produce depression rats model,the priority guizhi decoction for depression rats as follows:(1)the influence of behavioral indicators(weight,sugar water preference index,open-field score).(2)indicators of myocardial injury(serum CK-MB,BNP content,light microscopic morphology of myocardial cells);(3)indicators of oxidation and apoptosis(contents of SOD,MDA,Bax,Bcl-2 and mitochondrial electron microscopy in myocardial tissue);(4)cardiac autonomic nervous function index(tyrosine hydroxylase and electrocardiogram),in order to provide theoretical support and scientific basis for clinical application of guizhi decoction in the treatment of depression-related heart diseases.Objective:to observe the effects of guizhi decoction on anti-depression,myocardial cell protection and cardiac function in CUMS depression model rats,and to clarify the cardiac protection effect of huyingwei method on chronic stress depression rats,so as to provide an important theoretical basis for the treatment of depression-related heart diseases by huyingwei method.Methods:1.Preliminary study on the anti-depression and myocardial protection mechanism of guizhi decoction in CUMS depression model rats.The CUMS method was used for 28 days to establish the depression rat model.At the same time,guizhi decoction and positive drug(coenzyme Q10)were given to the rats continuously for 28 days.28 days to determine weight,sugar water preference index,open-field score,evaluation of depression groups of animals,the serum CK-MB and BNP,heart pathological evaluation of depression model rats cardiac damage,by Masson staining method to observe the depression model of rat myocardial cell structure,at the same time explore guizhi decoction for depression and protective effect and its mechanism of the damaged heart muscle.2.Preliminary study on the anti-oxidation and anti-apoptosis effects of guizhi decoction on depression model rats.The changes of SOD,MDA,Bax and Bcl-2 in the myocardial tissues of rats in the normal group,model group,coenzyme Q10 group and guizhi decoction group were measured to explore the protective mechanism of guizhi decoction on the anti-oxidative and anti-apoptotic mechanisms of the injured myocardium of the depressed model rats.3.Preliminary study on the effect of guizhi decoction on regulating autonomic nervous function in depression model rats.The content of tyrosine hydroxylase in rat cardiac myocytes was detected by immunohistochemical method,and the heart rate(rhythm)was observed by electrocardiogram,to explore the mechanism of guizhi decoction in regulating cardiac autonomic nervous function in rats with depression.Results:1.The effect of guizhi decoction on anti-depression and protection of damaged myocardium in CUMS depression model rats(1)after 28 days of modeling,the body weight,open-field score and glycemic water preference index of the depression model group were significantly decreased compared with the normal group(P<0.001,P=0.021,P<0.001),suggesting that the CUMS model successfully simulated depression.Compared with the depression model group,the open field score of guizhi decoction group was significantly higher than that of the depression model group(P=0.007).(2)compared with the normal group,the serum CK-MB and BNP in the model group,coenzyme Q10 group and guizhitang group were significantly increased(P<0.001,P=0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001).Compared with the model group,the serum CK-MB content and BNP content in the coenzyme Q10 group were significantly reduced(P=0.001)and decreased(P<0.001).Compared with the model group,the contents of CK-MB and BNP in the rats of guizhi decoction group were significantly decreased(P<0.001,P<0.001).The contents of CK-MB and BNP in serum of rats in guizhi decoction group were significantly lower than those in coenzyme Q10 group(P=0.011,P<0.001).(3)HE staining results indicated that the myocardial cells in the normal control group were neatly arranged with clear transverse and longitudinal stria,and the myocardial fibers were orderly arranged without fracture or defect,with normal nuclear morphology and size,uniform cytoplasm,and no exudation or cell edema.In the depression model group,edema and vacuolar granular degeneration were observed,intercellular space was widened and swollen,transverse and longitudinal stria could not be clearly seen,myocardial fiber was broken or defective,nuclear pyresis,cytoplasm was not uniform,and inflammatory cell infiltration was observed in myocardial interstitium.In guizhi decoction group,myocardial cells were arranged in a relatively orderly pattern with relatively normal morphology.Transverse and longitudinal striae could be seen,with a small amount of exudation,and myocardial fiber rupture or defect could be seen.The cardiomyocytes in the coenzyme Q10 group were arranged relatively regularly,with transverse and longitudinal striations,a small amount of exudation,uneven staining and rupture defects.(4)the results of Masson staining showed that the myocardial tissue of the normal group was red with neat arrangement and no collagen fibers appeared in the field of vision.In the model group,there were fibrotic changes,scarring,few residual myocardial tissues,uneven distribution of myocardial cells,and severe structural damage in the marginal area.Compared with the model group,the degree of myocardial fibrosis was reduced in guizhitang group and coenzyme Q10 group,the area of collagen fiber was significantly reduced,and there were many new blood vessels around the remaining myocardial cells.2.Antioxidant and anti-apoptotic effects of guizhi decoction on injured myocardium of depressed model rats(1)compared with the normal group,the SOD activity in the myocardial tissue of the model group was decreased(P=0.004).Compared with the model group,SOD activity of coenzyme Q10 group was increased(P=0.013),while that of guizhitang group was not significantly increased(P=0.902).(2)compared with the normal group,MDA in the myocardial tissue of the coenzyme Q10 group was significantly increased(P=0.026).Compared with the model group,the MDA of guizhi decoction group decreased significantly(P=0.001).(3)there was no significant difference in the levels of Bax and Bcl-2 between the four groups(P>0.05).(4)the results of electron microscopy suggested that the myocardial cells in the normal control group were arranged in regular order,and the mitochondria showed aggregation,neat distribution and normal morphology.The myocardial cells in the model group were irregular in arrangement,the mitochondria were scattered and disordered,the myocardial segments were partially inserted,the morphology was abnormal,and the mitochondrial crest was swollen.The myocardial cells in guizhi decoction group were arranged in a regular manner,and the mitochondria were clustered,mainly distributed around myocardial segments,with irregular morphology and mild mitochondrial crest swelling.The myocardial cells in the coenzyme Q10 group were arranged in a regular manner,with mitochondrial aggregation but irregular distribution,mainly distributed around myocardial segments,irregular morphology,and mild mitochondrial crest swelling.3.Regulating effect of guizhi decoction on autonomic nervous function of depression model rats(1)there was no significant difference in TH content between the groups(P>0.05).(2)the results of TH observation by immunohistochemical staining showed that the myocardial cytoplasm of rats in the normal group had dense and uniformly distributed TH positive cells with brown and black granules,and the myocardial cells were arranged neatly.In the depression model group,the dense brown and black particles in the cytoplasm of the cardiac myocytes were significantly increased,the color was deepened,and the cardiac myocytes were broken or damaged.In the coenzyme Q10 group,the dense brown and black particles in the cytoplasm of rat cardiac myocytes were more uniformly stained,the number of which was less than that in the depression model group,and the myocardium was more orderly arranged.In guizhitang group,dense brown and black granules were observed in the cytoplasm of myocardial cells,and the myocardium was well arranged.(3)after 28 days of CUMS modeling,frequent ventricular premature beats could be detected in rats of the model group,and atrial fibrillation could be observed in rats of guizhi decoction group.Conclusion:this experimental CUMS model is adopted to establish the depression model rats,evaluated the cassia twig decoction for depression rat myocardial injury protection,results show that the method of harmonic camp guard at the same time of antidepressant,the heart has a certain protective effect,its curative effect mechanism mainly to reduce the serum markers of myocardial injury,inhibiting myocardial fibrosis cells,promote new angiogenesis,reducing oxidative stress,reduce mitochondrial damage. |
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