| Purpose:In this experiment,male healthy SD rats were successively induced to form depression by CUMS and ischemic coronary heart disease by injecting isoproterenol hydrochloride.The model of depression combined with coronary heart disease was established.The effects of Electroacupuncture on the expression of oxidative stress related indexes GSH and mitochondrial autophagy related protein beclin-1 in the model of depression combined with coronary heart disease were observed,and the mechanism of electroacupuncture in the treatment of depression combined with coronary heart disease was explored,To verify the therapeutic effect of Electroacupuncture on the combined disease of the two.Material and method:Take 100 healthy male SD rats,first carry out adaptive feeding for 3 days,and carry out weight weighing,open field test,behavioral index detection and ECG detection of sugar water bias test for each rat respectively.Then 80 rats with similar comprehensive scores are included in the experiment.The selected 80 rats were randomly divided into 8 groups with 10 rats in each group.The random number table method was used for grouping.Each group was divided into blank group,depression model group,coronary heart disease model group,compound model group,depression model escitalopram group,depression model acupuncture group,compound model sertraline group and compound model acupuncture group.The modeling lasted for 28 days.Except the blank group and coronary heart disease group,the other 6 groups were given cums during the modeling period,and were randomly stimulated every day to induce the depression model.Coronary heart disease model,compound model group,compound model sertraline group and compound model acupuncture group were fed in a normal way in the first stage(days 1-26),and isoproterenol hydrochloride was injected in the second stage(days 27-28)to induce ischemic coronary heart disease model.The treatment lasted for 21 days.The rats in the depression model acupuncture group and the compound model acupuncture group were respectively bound and fixed on the self-made rat fixator to make them relatively quiet,and the specification was 0.18 mm × 25 mm "Huatuo brand" acupuncture needle,with reference to the acupoint positioning method of rats in animal experiment,select the corresponding acupoints on its body surface for acupuncture.The acupoints are Baihui,Taichong,Neiguan,Zusanli and Sanyinjiao.The acupuncture depth of each acupoint is about 2mm under the skin.The frequency of the electroacupuncture instrument was set to 2Hz and the current was set to 0.6ma.The wave type was density wave.The power on intensity was based on the slight tremor of the limbs of the rats equivalent to the set frequency.The other six groups of rats were simply bound and fixed once every two days for 15 minutes.Escitalopram group of depression model and sertraline group of compound model were perfused with escitalopram 0.2mg/100 g and sertraline 1mg / 100 g respectively,and the other six groups were perfused with the same amount of normal saline.The above modeling and treatment operations are performed regularly every day.At the end of modeling and treatment,the behavioral indexes and ECG of each rat were detected again,and then the rats were killed and taken materials,and the corresponding detection methods were adopted to detect the indexes.Results:1 Comparison of general state of rats in each group during interventionDuring the three-day adaptive feeding period,the rats were in excellent condition,flexible in response and quick in action.They could drink,eat and defecate normally.Their hair color was white and bright,their weight increased relatively,and there was no death.During the first stage of modeling(days 1-26),the rats in the blank group and the coronary heart disease model group had no abnormal changes compared with before.After cums stimulation,the rats in other groups may have poor state,slow response,slow action,gray hair color and so on.In the second stage(day 27-28),the rats in coronary heart disease model group,compound model group,compound model sertraline group and compound model acupuncture group were injected with IOS,or the mouth,tongue,nose and claws gradually turned blue.After western medicine or acupuncture intervention,the above conditions were improved in the depression model escitalopram group,depression model acupuncture group,compound model sertraline group and compound model acupuncture group.2.Weight changes of rats in each groupAt the end of each stage of the experiment,the body weight of rats in each group was recorded and the changes were observed.The comparison showed that the body weight of each rat increased during the adaptive feeding period before modeling.After cums modeling,compared with the blank control group,except the coronary heart disease model group,the body weight of the other six groups decreased,and the results were statistically significant(P< 0.05).After corresponding treatment,compared with the blank group,the weight of the coronary heart disease model group did not change significantly(P > 0.05),and the weight of the remaining six groups decreased significantly(P < 0.05).Compared with the depression model group,the weight of rats in the depression model escitalopram group and depression model acupuncture group increased significantly(P < 0.05).Compared with the compound model group,the weight of rats in the compound model sertraline group and the compound model acupuncture group increased significantly(P < 0.05).3.Changes of open field test scores of rats in each groupAfter each stage of the experiment,the open field test scores of rats in each group were recorded and the changes were observed.The comparison showed that after cums modeling,compared with the blank control group,except the coronary heart disease model group,the open field test scores of the other six groups decreased,and the results were statistically significant(P < 0.05).After treatment,compared with the depression model group,the decreasing trend of open field test score of depression model estalopram group and depression model acupuncture group was significantly increased,and the results were statistically significant(P < 0.05).Compared with the compound model group,the open field test scores of the compound model sertraline group and the compound model acupuncture group were significantly increased,and the results were statistically significant(P < 0.05).4.Changes of sugar water preference of rats in each groupAt the end of each stage of the experiment,the preference of rats in each group was recorded and the changes were observed.The comparison showed that in the adaptive feeding stage before modeling,there was no significant difference in sugar water preference among rats in each group(P > 0.05).After modeling,compared with the blank group,except the coronary heart disease group,the preference of sugar water in the other six groups decreased significantly(P < 0.05).There was no significant difference in the degree of depression between the acupuncture group and the compound model group(P < 0.05).Compared with the depression model group,the sugar water preference of the depression model escitalopram group and the depression model acupuncture group increased significantly(P < 0.05).Compared with the compound model group,the sugar water preference of rats in the compound model sertraline group and the compound model acupuncture group increased significantly(P < 0.05).5 Changes of ECG S-T wave voltage of rats in each groupAt the end of each stage of the experiment,the ECG of rats in each group was intercepted and the changes were observed.The comparison showed that there were no abnormal changes in ECG of rats in each group after cums modeling.After the rats were induced by injection of isoproterenol,the S-T segment of coronary heart disease model group,compound model group,compound model sertraline group and compound model acupuncture group all moved downward,with an obvious trend,while there was no significant change in ECG in depression model group.6 Morphological changes of hippocampus and myocardium in each group6.1 Morphological changes of hippocampus in each groupHE staining of rat hippocampal tissue sections showed that the neuronal cell bodies of the blank group and the coronary heart disease model group were arranged orderly and showed multi-layer distribution.Compared with the blank group: the arrangement of neuronal cells in depression model group and compound model group became disordered and the spacing increased.The depression model escitalopram group,depression model acupuncture group,compound model sertraline group and compound model acupuncture group were arranged neatly,with a little damage to the nucleolus and slight pathological changes.6.2 Morphological changes of myocardium in each groupHE staining of rat myocardial tissue sections showed that no abnormal changes were found in the myocardial tissue structure of the blank group,and a small amount of myocardial fibers in the depression model group shrank,and capillaries dilated and congested.In the coronary heart disease model group and the compound model group,the myocardial tissue fibers proliferated,the gap became more loose,the myocardial cells were damaged or even necrotic,the capillaries proliferated,and the connective tissue became more loose.Compared with the depression model group,the pathological changes in myocardial fibers in the depression model escitalopram group and the depression model acupuncture group were improved,and the changes were more significant.Compared with the composite model group,the composite model sertraline group and the composite model acupuncture group had a small amount of myocardial fiber proliferation,gap enlargement,cell injury and necrosis,capillary proliferation,connective tissue loosening and other phenomena,and the changes were not obvious.7 Changes of serum GSH expression in rats in each groupCompared with the blank group,the expression of serum GSH in depression model group,coronary heart disease model group and compound model group decreased significantly(P <0.05).Compared with the coronary heart disease model group,the expression of serum GSH in the depression model group did not change significantly(P > 0.05),but decreased significantly in the compound model group(P < 0.05).Compared with the depression model group,the expression of serum GSH in the depression model escitalopram group and depression model acupuncture group was significantly higher(P < 0.05),but there was no significant difference between the two treatment groups(P > 0.05).Compared with the compound model group,the expression of serum GSH in the compound model sertraline group and the compound model acupuncture group increased significantly(P < 0.05).However,there was no significant difference between the two groups(P > 0.05).8 Changes of beclin-1 protein expression in hippocampus of rats in each groupProtein bands and gray values showed that compared with the blank group,the expression of beclin-1 protein in hippocampus of rats in coronary heart disease model group did not change significantly(P > 0.05),while the expression of beclin-1 protein in hippocampus of rats in depression model group and compound model group decreased significantly(P < 0.05).Compared with coronary heart disease model group,the expression of beclin-1 protein in hippocampus of depression model group and compound model group decreased(P < 0.05),and the decrease in compound model group was significant(P < 0.05).Compared with depression model group,the expression of beclin-1 protein in hippocampus of depression model escitalopram group and depression model acupuncture group increased(P < 0.05),but there was no significant difference between the two groups(P > 0.05).Compared with the compound model group,the expression of beclin-1 protein in hippocampus of rats in the compound model sertraline group and the compound model acupuncture group were significantly increased(P < 0.05),but the change of protein expression between the two groups was not significant(P > 0.05).Conclusion:1 When rats with depression complicated with coronary heart disease,the expression of GSH in serum decreased significantly,and the expression of beclin-1 protein in hippocampus also decreased significantly,which inhibited the level of mitochondrial autophagy and enhanced the level of oxidative stress,leading to the occurrence of depression complicated with coronary heart disease.2 after electroacupuncture stimulation at Baihui Point,Taichong Point,Neiguan point,Zusanli point and Sanyinjiao point,the expression of serum GSH increased significantly,and the expression of beclin-1 protein in hippocampus also showed an obvious upward trend,indicating that acupuncture at the above points has an obvious therapeutic effect on the disease,which is closely related to the level of mitochondrial autophagy and oxidative stress. |
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