Construction Of A Mice Model Of Depression With Deficiency Of Heart And Spleen And Study On The Intervention Effect Of Guipi Decoction

Objective:By using a modified plantar electroshock method combined with weight-bearing swimming techniques,an animal model of depression with syndrome combination of heart and spleen deficiency was established.The application of Guipi Decoction intervention provides a stable and reliable animal model for the study of depression related syndrome types,expands the scope of traditional Chinese medicine for the prevention and treatment of depression,and provides an experimental basis for the development of drugs for the prevention and treatment of depression with both heart and spleen deficiency.Method:1.In this study,complete the construction of mice model by improved foot electric shock combined with weight-bearing swimming.To compare the efficacy of this model with the more commonly used CUMS model in Western medicine.We divided the experimental mice into five groups: Control,M1(CUMS),P1(CUMS model with paroxetine administration),M2(modified plantar electroshock combined with weight-bearing swimming),and P2(modified plantar electroshock combined with weight-bearing swimming with paroxetine administration).Each group consisted of 9mice.The CUMS modeling method was used to model M1 and P1 groups,and the improved foot electric shock combined with weight-bearing swimming was used to model M2 and P2 groups.The apparent validity,structural validity,and effectiveness of the mice were tested to assess the depressive status of the mice;By detecting the indicators of deficiency of qi and blood in the heart and spleen of mice,the situation of deficiency of both heart and spleen in mice was judged,and the differences in the effects of depression and deficiency of both heart and spleen in mice animal models made by the two modeling methods were compared.2.Guipi Decoction was used to measure the syndrome by prescription,and the therapeutic effect of Guipi Decoction was studied.The experimental mice were divided into control group(Control),Guipi low-dose group(Guipi L),Guipi medium-dose group(Guipi M),Guipi high-dose group(Guipi H),and paroxetine group(Paroxetine),with 9 mice in each group.After the experiment,we evaluated the effect of each drug on depression associated with heart and spleen deficiency.Result:1.After modifying the modified plantar electroshock and weight-bearing swimming method to produce depression in mice,various indicators of mice were tested.The evaluation results of the general state of mice show that the body weight(P<0.05)decreased in the M2 group,and the M2 group also had a significant decrease in food intake on the 18 th day of the experiment(P<0.05),while there was not in the M1 group.There was not in water intake in both groups.Both the M1 group(P<0.05)and M2 group(P<0.01)had an increased percentage of Wake time,while a decreased percentage of NREM time(P<0.05 for M1 group and P<0.01 for M2 group)and REM time(P<0.05 for M1 group and P<0.01 for M2 group)was observed.The detection results of depression indicators in mice showed that the SPT index decreased in both the M1 group(P<0.01)and M2 group(P<0.01).The total time spent in the center of the OFT decreased in both the M1 group(P<0.01)and M2group(P<0.01),as did the total number of entries into the center of the OFT(P<0.05 for M1 group and P<0.05 for M2 group).In addition,the immobility time in the FST increased in both the M1 group(P<0.01)and M2 group(P<0.01),as did the immobility time in the tail suspension test(P<0.01 for M1 group and P<0.05 for M2group).The levels of serotonin were reduced in the brain tissue(P<0.01)and serum(P<0.01)of both the M1(P<0.01)and M2(P<0.05)groups,as well as the levels of dopamine in the brain tissue(P<0.01)and serum(P<0.01)of both the M1(P<0.01)and M2(P<0.01)groups.The corticosterone levels increased in the brain tissue(M1group: P<0.05;M2 group: P<0.01)and serum(M1 group: P<0.01;M2 group: P<0.001)of both the M1 and M2 groups.The detection results of the indicators of heart and spleen deficiency in mice show that the tongue color saturation of the M2 group decreased(P<0.05),and the diameter of the neck artery during diastole narrowed in both the M1(P<0.05)and M2(P<0.01)groups.The diameter of the neck artery during systole also narrowed in both the M1(P<0.05)and M2(P<0.05)groups,and the maximum blood flow velocity of the neck artery decreased in the M1(P<0.01)and M2(P<0.01)groups.The left ventricular ejection fraction decreased in both the M1(P<0.05)and M2(P<0.01)groups,and the mean cerebral blood flow decreased in both the M1(P<0.05)and M2(P<0.01)groups.The SOD content in the myocardial tissue decreased in both the M1(P<0.05)and M2(P<0.01)groups,while the MDA content increased in both the M1(P<0.05)and M2(P<0.01)groups.Spleen index(P<0.05)、GAS levels(P<0.01)and D-xylose(P<0.05)level decreased in the M2 group,but not in the M1 group.This indicates that mice stimulated by modified plantar electroshock and weight-bearing swimming method exhibited symptoms of depression and deficiency of both heart and spleen.2.The efficacy of the low(Guipi L),medium(Guipi M)and high(Guipi H)dose groups of Guipi Decoction and the paroxetine group were compared.The evaluation results of general indicators show that there were no differences in body weight,food intake and water intake among the groups;the percentage of Wake time in mice in the Guipi M group(P<0.05)and Guipi H group(P<0.05)decreased,the percentage of REM time in mice in the Guipi M group(P<0.05)and Guipi H group(P<0.05)increased,and the percentage of NREM time in mice Guipi M group(P<0.05)and Guipi H group(P<0.05)increased percentage of NREM time in mice,no difference was observed in other groups.The detection results of depression indicators in mice showed that increased index of sugar-water preference in mice in the Guipi H group(P<0.05)and paroxetine group(P<0.05).Guipi M group(P<0.05),Guipi H group(P<0.05)and paroxetine group(P<0.01)increased the total number of times mice entered the centre of the open field and the total time;mice in the high-dose group(P<0.01)and the paroxetine group(P<0.01)of Guipi Decoction had reduced resting time in the TST;mice in the high-dose group(P<0.01)and the paroxetine group(P<0.001)of Guipi Decoction had reduced resting time in the FST;The content of5-HT in the brain tissue of mice in the Guipi H group(P<0.05)and paroxetine group(P<0.01)increased,the content of 5-HT in the serum of mice in the Guipi M group(P<0.01)Guipi H group(P<0.01)and paroxetine group(P<0.01)increased,and the content of DA in the Guipi H group(P<0.05)and paroxetine group(P<0.01)increased,Cor content in brain tissue of mice in Guipi H group(P<0.05)and paroxetine group(P<0.01)decreased,while that in serum of mice in Guipi H group(P<0.05)and paroxetine group(P<0.05)decreased;The detection results of the heart and spleen deficiency syndrome indicators in mice show that an increase in reddening of the tongue sheath in the Guipi M and Guipi H groups(P<0.05).The diameter of carotid dilatation increased in the Guipi H group(P<0.05),the diameter of carotid constriction increased in the medium-and high-dose groups(P<0.01),and the mean cerebral BFI increased in the high-dose group(P<0.05)and paroxetine groups(P<0.05);The SOD content of myocardial tissues of mice in the Guipi H group(P<0.05)and paroxetine group(P<0.05)increased;the MDA content of myocardial tissues of mice in the Guipi H group(P<0.05)and paroxetine group(P<0.05)decreased;the spleen index of mice in the Guipi H group(P<0.05)increased;The serum D-xylose(P<0.01)and GAS(P<0.05)level of mice was increased in the Guipi H group.This indicates that Guipi Tang has a significant effect on improving depression of both heart and spleen deficiency type.Conclusion:1.By the modified plantar electroshock and weight-bearing swimming method,a mice model of depression with deficiency of both heart and spleen was successfully constructed,which conforms to the characteristics of combining disease and syndrome,and enriches the types of animal models of combining disease and syndrome in depression.2.By observing the intervention effect of Guipi Decoction,it was found that it has a significant antidepressant effects,and it has more significant effects on improving the indicators of both heart and spleen deficiency syndrome(such as cerebral blood flow,spleen index,gastrin,sleep status,etc.)in mice,demonstrating the advantages of traditional Chinese medicine in antidepressant treatment.The "prescription based syndrome" verified the reliability of the mice model of combining this disease and spleen deficiency syndrome.