| Objective: In this experiment,the rats with depression and coronary heart disease were taken as the experimental objects,and the changes of relevant indexes in each group were observed.To compare the difference of intervention effects of different schemes in the course of treatment,explore the biological mechanism of acupuncture treatment of depression combined with coronary heart disease,and provide scientific experimental data for clinical treatment of depression and cardiovascular related diseases.Materials and Methods: Fifty healthy male SD rats,weighing 180~220 g,were fed adaptively in the animal experiment center for 3 days.The 40 SD rats with the most similar comprehensive score were selected according to their weight and other behavioral factors and randomly divided into blank group,model group,sertraline group and acupuncture group,with 10 rats in each group.Except for the blank group,the other groups were subjected to chronic unexpected mild stimulation(CUMS)modeling for 28 days.On the 27 th and 28 th day,the white group was anesthetized by intraperitoneal injection of 0.3 ml/100 g of normal saline,and the other groups were anesthetized by intraperitoneal injection of 10% chloral hydrate solution at 0.3 ml/100 g,and the multi-point subcutaneous injection of 8.5 mg/100 g of isoproterenol hydrochloride was used to construct the model of bicardiopathy.After successful modeling,the blank group continued to eat normally,and the other groups continued to use the CUMS method for repeated stimulation.At the same time,the rats in the sertraline group were given sertraline solution 1mg/100g/d by gavage,and the rats in the acupuncture group were respectively tied to the self-made rat fixation plate,and Huatuo brand acupuncture and moxibustion needles(0.18 × 25 mm).After about 2 mm of acupuncture at the points of Baihui,Neiguan,Zusanli,Sanyinjiao and Taichong,connect the electroacupuncture instrument and set the parameters as density wave,frequency 2 Hz,current 0.6 m A.Observe the slight vibration of rats’ limbs,15 minutes each time,once a day.The model group was only fixed for 15 minutes,without acupuncture,and was infused with normal saline according to their weight.The above operations were performed regularly every day for 21 consecutive days.During this period,various behavioral scores of rats were measured before,after and after treatment,including weight,preference for sugar water,forced swimming,immobility time,open field test,and electrocardiogram.After the treatment,the rats were anesthetized and killed and fixed on the operating table.Blood from abdominal aorta,hippocampus and heart tissue from ice were taken and fixed in polyformaldehyde and EP tubes for freezing.The expression level of NLRP3 protein in rat hippocampus was detected by WB technique,and the content of TXNIP and IL-18 in rat serum was detected by ELISA kit.Result:1.General condition and behavior of rats in each group during the intervention periodDuring the three-day adaptive feeding period,all rats were in good condition,flexible in response,quick in action,drinking,eating,urinating and defecating can be carried out normally,their hair color was white and shiny,their weight also increased,and no death occurred.After CUMS modeling,in the first stage of modeling(Day 1-26),the rats in the blank group were compared with those in the adaptive feeding stage.Except for the increase of body weight,there were no significant changes in the general state,drinking water,diet,bowel movement,etc.The rats in the other groups gradually became worse after CUMS stimulation,and the reaction was delayed.In the second stage(Day 27-28),after ISO injection,lips,tongue The nose and claws gradually turn purple.After western medicine or acupuncture and moxibustion,the general state of the sertraline group and the acupuncture group were improved.2.Body weight changes of rats in each groupAt the end of each stage of the experiment,the body weight of each group of rats was recorded and its changes were observed.The comparison showed that during the adaptive feeding period before modeling,the weight of all rats increased.After CUMS modeling,the weight of rats in the model group,sertraline group,acupuncture group decreased compared with the blank group,and the results were statistically significant(P<0.05);After treatment,compared with the model group,the weight of rats in the acupuncture group and the sertraline group showed an upward trend,and there was a significant difference in the increase(P<0.05);Compared with the sertraline group,there was no significant change in the acupuncture group(P>0.05).3.Changes of open field test scores of rats in each groupAfter the completion of each stage of the experiment,record the results of open-field test of rats in each group and observe the changes.The comparison showed that after the establishment of the CUMS model,compared with the blank group,the scores of the open field experiment of the rats in the model group,the sertraline group and the acupuncture group decreased,and the results were statistically significant(P<0.05);After treatment,the decline trend of open-field test results of rats in model acupuncture group and model sertraline group was significantly up-regulated,and the results were statistically significant(P<0.05),while there was no statistically significant difference acupuncture group and sertraline group(P>0.05).4.Changes of rat’s preference for sugar water in each groupAfter adaptive feeding,it was found that there was no significant difference in the preference of rats in each group for sugar water,and there was no statistical significance(P>0.05).After modeling,compared with the blank group,the preference of rats in the group,the sertraline group,and the acupuncture group for sugar water decreased significantly(P<0.05).After treatment,compared with the blank group,the preference of rats in the model group,the sertraline group and the acupuncture group for sugar water decreased significantly(P<0.05);Compared with the model group,the preference of sugar water in the sertraline group and the acupuncture group was significantly higher,and the difference was statistically significant(P<0.05).There was no significant difference acupuncture group and sertraline group(P>0.05).5.The change of forced swimming immobility time of rats in each groupAfter modeling,compared with the blank group,the model group,the sertraline group and the acupuncture group all showed an upward trend,and the results were statistically significant(P<0.05).After treatment,compared with the model group,the forced swimming immobility time of the sertraline group and the acupuncture group showed a downward trend,with a statistically significant difference(P<0.05).There was no significant difference acupuncture group and sertraline group(P>0.05).6.ECG changes of rats in each groupAfter 28 days of CUMS modeling,compared with the blank group,there were no significant changes in other groups.After the injection of isoproterenol,it was found that the ST segment of the model group,the sertraline group,and the acupuncture group all moved down significantly,indicating that the model was successful..7.Morphological changes of myocardial tissue and hippocampus of rats in each group7.1 Changes in cardiac histomorphology of rats in each groupHE staining of cardiac tissue sections of rats showed that there was no abnormal change in cardiac tissue structure of rats in the blank group.In the model group,the myocardial tissue fibers proliferated,the interstitium was soft,and the myocardial cells were damaged and necrotic in different degrees.Compared with the model group,the sertraline group and the acupuncture group showed a small amount of myocardial fiber hypertrophy,gap expansion,cell injury and necrosis,proliferation,loose connective tissue and other changes were not obvious.7.2 Morphological changes of hippocampus of rats in each groupThe nerve cell bodies of rats in the blank group were orderly arranged and distributed in multiple layers;Compared with the blank group,the arrangement of neurons in the model group became disorderly and the distance became larger;After treatment,the sertraline group and the acupuncture group were arranged in a relatively neat manner,with slight damage to the nucleus and mild lesions.8.Changes of TXNIP expression in serum of rats in each groupCompared with the blank group,the expression of TXNIP in the other groups was significantly higher(P<0.05).Compared with the model group,the expression of TXNIP in serum of rats in the sertraline group and the acupuncture group decreased significantly(P<0.05).Compared with the sertraline group,the expression of TXNIP in the serum of rats in the acupuncture group decreased significantly(P<0.05).9.Changes of IL-18 expression in serum of rats in each groupCompared with the blank group,the expression of IL-18 in other groups was significantly higher(P<0.05).Compared with the model group,the expression of IL-18 in serum of rats in the sertraline group and the acupuncture group decreased significantly(P<0.05).There was no significant difference the acupuncture group and the sertraline group(P>0.05).10.Changes of NLRP3 protein expression in hippocampus of rats in each groupCompared with the blank group,the expression of NLRP3 protein in the hippocampus of rats in the model group increased significantly(P<0.05).Compared with the model group,the expression of NLRP3 protein in the hippocampus of rats in the sertraline group and the acupuncture group decreased significantly(P<0.05).Compared with the sertraline group,the expression of NLRP3 protein in the hippocampus of rats in the acupuncture group decreased significantly(P<0.05).Conclusion:1.Acupuncture at Baihui,Neiguan,Zusanli and Taichong points inhibited the expression of TXNIP in rats’ serum and NLRP3 in rats’ hippocampus,suggesting that inflammation was reduced,and acupuncture treatment had a positive effect on anti-inflammation.2.Electroacupuncture has a good therapeutic effect on rats with bicardiopathy(depression combined with coronary heart disease). |