| Purpose:In this experiment,Chronic Unpredictable Mild Stress model(CUMS)was combined with subcutaneous injection of Isoprenephrine hydrochloride(ISO)to hydrochloride,The model rats of depression complicated with coronary heart disease were induced to copy,and the influence of electricity on key proteins of the classic pathway of cell scorch death in the hippocampus and heart tissue of the model rats was studied.Combined with the pathogenesis theory of liver qi stagnation,qi stagnation and blood stasis,stagnation and fire of traditional Chinese medicine,the pathogenesis and treatment principle of inflammation and depression complicated with coronary heart disease were explored from the level of cell scorch death.Material and method:Fifty healthy male SPF SD rats,with the body weight of175--225 g,were selected after 3 days of adaptive feeding,and 40 rats with similar behavioral scores were randomly divided into blank group,model group,Sertraline group and acupuncture group.Except the blank group,CUMS was administered for28 days in the other 3 groups,during which isoproterenol hydrochloride was repeatedly injected subcutaneously after anesthesia at the 27 th and 28 th days to establish a model of depression combined with coronary heart disease.After successful modeling,the rats in blank group,model group and acupuncture group were given normal saline intragastric administration at the dose of 1mg/100 g at 8 o’clock every day.Sertraline group rats were given sertraline solution intragastric at the dose of 1mg/100 g.For the rats in the acupuncture group,0.18mm*25mm "Huatao brand" acupuncture was used to inject into the subcutaneous points of Baihui,Neiguan,Shenmen and Taichong.The electroacupuncture instrument was connected,and the density wave was applied with a frequency of 2-20 Hz and a current of about2-3m A.The intensity was defined as slight tremor in the front and rear limbs of the rats consistent with the frequency of electroacupuncture.Blank group,model group and Sertraline group were also bound with fixed plates for 15 min.Four behavioral scores were performed on each rat at three time points before modeling,after modeling,before treatment and after treatment,namely,body weight,open field experiment,immovable time of forced swimming,and sugar water bias.The blood of abdominal aorta,hippocampus and heart of rats in each group were collected for internal fixation or cryopreservation.The expression levels of Caspase-1 and GSDMD in rat heart and hippocampus were detected by Western Blot,and serum IL-1β was detected by ELISA.Results:1.Changes in body weight of ratsAfter CUMS modeling,compared with blank group,the body weight of rats in all groups was decreased to different degrees(P<0.05).After taking corresponding measures,the body weight of rats in acupuncture group and Sertraline group increased significantly compared with model group,with statistical significance(P<0.01).But compared with Sertraline group,the body weight of rats in acupuncture group was not significantly changed(P > 0.05).2.Test results of sugar water bias of rats in each groupAfter CUMS modeling,compared with blank group,the bias of sugar water in the other three groups decreased significantly(P<0.01),and the bias of sugar water was almost the same as that of pure water,but there was no significant difference in the bias of sugar water among the three groups.After taking corresponding measures,compared with model group,Sertraline group and acupuncture group had significantly improved the bias to sugar water,and the results were statistically significant(P<0.01).However,compared with Sertraline group,there was no significant change in bias of sugar water in acupuncture group(P > 0.05).3.Visual images of total score and track in open field experiment of rats After CUMS modeling,the open field test scores of other groups were significantly decreased compared with blank group(P<0.01).After treatment,compared with model group,the open field test scores of Sertraline group and acupuncture group were significantly improved,with statistical significance(P<0.01).But compared with Sertraline group,the open field test score of rats in acupuncture group had no significant change(P > 0.05).Visualized trajectories of each group showed that rats in the blank group walked around,while rats in the model group only stayed in one corner.After treatment,rats returned to walking around.4.Experimental results of forced swimming in ratsAfter CUMS modeling,compared with blank group,the swimming time of the other three groups was significantly increased(P<0.01),and there was no significant difference among the three groups.After treatment,the immobile time of rats in Sertraline group and acupuncture group was significantly reduced compared with model group,with statistical significance(P<0.01).But compared with Sertraline group,there was no significant change in the time of swimming in acupuncture group(P > 0.05).5.Changes of electrocardiogram in ratsAfter ISO injection,the rats in the model group,Sertraline group and acupuncture group showed continuous ST segment elevation and significantly increased Q-wave amplitude and other obvious myocardial infarction.6.Morphological changes of rat hippocampal tissue and myocardial tissue After HE staining,the number of neurons in the DG region of the hippocampus of rats in blank group was abundant,closely arranged,with thick cell layer,clear cell outline,regular morphology and structure,round nuclei in the center,nucleoli clearly visible,and no obvious pathological changes.In the model group,the number of neuron cells decreased significantly,the intercellular space was enlarged,the arrangement was loose and disordered,the cell layer was obviously thinner,a large number of nuclei were contracted and necrotic,the nuclei were deeply stained,and some cells showed swelling and deformation.Compared with Sertraline group and model group,the number of neuron cells increased significantly,the arrangement returned to order,the number of cell layers increased,the cell shape returned to normal,but there were still some necrotic cells.In blank group,the myocardial cells were arranged tightly and orderly with complete structure,and the nucleus ellipse was located in the middle of the cell,consistent with the direction of myofibril,without obvious pathological changes.In the model group,large myocardium cells were damaged and necrotic,nucleus disappeared,myocardial cells were broken transverse,intercellular space increased,and there was a large number of inflammatory cell infiltration,mainly including neutrophils,macrophages and lymphocytes,as well as capillary hyperplasia and congestion,suggesting the presence of myocardial ischemia.Compared with the blank group,the acupuncture group and Sertraline group showed pathological changes and inflammatory cell infiltration,but compared with the model group,the inflammatory lesions were greatly improved,the nuclei disappeared and the interstitial congestion were also relieved.The improvement of myocardial tissue morphology and structure in acupuncture group was more obvious than that in Sertraline group.7.Serum inflammatory factor IL-1β content in 7 ratsAfter treatment,compared with blank group,serum IL-1β content in the other three groups was increased to varying degrees(P<0.05).Compared with model group,serum IL-1β content in Sertraline group and acupuncture group was significantly decreased,and the results were statistically significant(P<0.01).But compared with Sertraline group,the serum IL-1β content in acupuncture group had no significant change(P > 0.05).8.Expression levels of Caspase-1 and GSDMD in rat hippocampus After treatment,compared with blank group,the expression levels of Caspase-1 and GSDMD in hippocampal tissues of the other three groups were increased to varying degrees(P<0.05).Compared with model group,the expressions of Caspase-1 and GSDMD in the heart tissues of Sertraline group and acupuncture group were decreased,with statistical significance(P<0.05).There was no significant difference between Sertraline group and acupuncture group(P > 0.05).9.Expression levels of Caspase-1 and GSDMD in rat heart tissue After the treatment,compared with the blank group,the expressions of Caspase-1 and GSDMD in the heart tissues of the other three groups were significantly increased to varying degrees(P<0.01).Compared with model group,the expressions of Caspase-1and GSDMD in the heart tissues of Sertraline group and acupuncture group were significantly decreased,with statistical significance(P<0.01).There was no significant difference between Sertraline group and acupuncture group(P > 0.05).Conclusion:1.Electroacupuncture therapy has a good therapeutic effect on depression complicated with coronary heart disease.2.Electroacupuncture can inhibit the expression of Caspase-1/GSDMD,a key protein in the classical pathway of pyrodeath,thereby reducing the release of inflammatory factor IL-1 β and reducing the occurrence of inflammatory response to produce therapeutic effects. |
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