Mechanisms Of Acupuncture And Moxibustion At Daling And Shangxing Points By Ameliorating Depression-like Behaviors In Chronic Unpredictable Mild Stress Rats

Background:Depression is a major mood disorder.Most antidepressants have poor efficacy and large side effects.It is necessary to seek a safe and effective alternative therapy for depression.Thirteen ghost points are the experiential points of acupuncture and moxibustion in the treatment of psychosis.Modern research also confirms that thirteen ghost points have a unique effect on depression and other mental diseases,but its mechanism is not fully elucidated.Objective:To observe the effects of acupuncture and moxibustion of Daling(PC7)and Shangxing(DU23)from 13 ghost points reversing the behaviour changes,serotonin neurotransmitter(5-HT),LHb β-CaMKII,nitric oxide and guanosine cyclophosphate(NO-cGMP)signal pathway of chronic unpredictable mild stress(CUMS)depression model rats,thus discuss the antidepressant mechanism of "Daling" and "Shangxing"points.1.Using the behavioral methods of sucrose preference test(SPT),the open field test(OFT),and the elevated plus maze(EPM),we observed the effect of acupuncture and moxibustion on "Daling" and "Shangxing" points on the depression like behavior of CUMS model rats.2.To detect the contents of serotonin neurotransmitters in hippocampus,prefrontal cortex and serum samples of rats,we explore the effect of acupuncture and moxibustion on "Daling" and "Shangxing" points on the central nervous system 5-HT of CUMS model rats.3.To detect the expression of β-CaMKII protein and mRNA in lateral habenula samples of rats,we explore the effects of acupuncture and moxibustion on "Daling"and "Shangxing" points on LHb β-CaMKII of CUMS model rats.4.To detect the changes of NO and cGMP contents in hippocampus and plasma samples of rats and the expression of iNOS,nNOS,NR1,NR2A and NR2B mRNA in hippocampus,we explore the effects of acupuncture and moxibustion on "Daling" and"Shangxing" points on NO-cGMP signal pathway of CUMS model rats.Methods:60 Male Sprague Dawley rats were divided into the control group(C),the model group(M),the acupuncture points group(AP),the acupuncture non-points group(AN),the moxibustion points group(MP)and the moxibustion non-points group(MN),with 10 rats in each group.The rat model was established by chronic unpredictable mild stress for 42 days.The intervention groups were given 21 days of treatment using acupuncture and moxibustion on "Daling" and "Shangxing" points.Rats weight were monitored regularly,behaviors associated with depression were tested using the sucrose preference test,the open field test,and the elevated plus maze test.Enzyme-linked immunoassay(ELISA)was used to detect the contents of 5-HT in hippocampus,prefrontal cortex and serum samples;the contents of Nitric oxide(NO)and Cyclic guanosine monophosphate(cGMP)in hippocampus and plasma were detected by ELISA;Reverse transcription-polymerase chain reaction(RT-PCR)were used to detect the expression of inducible nitric oxide synthase(iNOS),neuronal nitric oxide synthase(nNOS),and the N-methyl-D-aspartate(NMDA)receptor subunits,NR1,NR2A,and NR2B in the rat hippocampus;Western Blot(WB)and qPCR were used to detect the expression of β-CaMKⅡ protein and mRNA in lateral habenula.Results:1.Compared with the control group,the weight growth,sucrose preference test,the open field test,and the elevated plus maze scores of the model group were all decreased(P<0.05);Compared with the model group,acupuncture and moxibustion on "Daling" and "Shangxing" points can effectively reverse the changes of body weight and behavior tests of depression rats(P<0.05).2.Compared with the control group,the content of 5-HT in hippocampus,prefrontal cortex and serum of the model rats decreased significantly(P<0.01);Compared with the model group,the content of 5-HT in acupuncture point and moxibustion point group increased(P<0.05).3.Compared with the control group,the level of β-CaMKII protein and mRNA in the lateral habenula of the model rats increased significantly(P<0.05);Compared with the model group,the level of LHb β-CaMKII protein and mRNA in acupuncture point and moxibustion point group decreased(P<0.05).4.Compared with the control group,the content of NO and cGMP in the hippocampus and plasma of the model rats increased significantly(P<0.01),and the expression of NR1,nNOS,iNOS,NR2A and NR2B mRNA in hippocampus also increased(P<0.01);Compared with the model group,the content of NO and cGMP in the hippocampus and plasma of acupuncture point and moxibustion point group decreased(P<0.05),the mRNA of NR1,nNOS,iNOS,NR2A and NR2B in the hippocampus of acupuncture point rats decreased(P<0.05),and the mRNA of NR1,iNOS,NR2A and NR2B in the hippocampus of the moxibustion point group rats decreased(P<0.05).Conclusions:Acupuncture and moxibustion of "Daling" and "Shangxing" from"Thirteen ghost points"can reverse the weight growth trend and depression like behavior changes of CUMS rats,which shows that acupuncture and moxibustion of "Daling"and"Shangxing" is effective in the treatment of depression.The antidepressant mechanism of acupuncture and moxibustion on the "Daling"and "Shangxing"points may be related to the following effects:increasing the content of 5-hydroxytryptamine neurotransmitter in hippocampus,prefrontal cortex and serum samples of depression model rats;decreasing the over expression of-CaMKII protein and mRNA in the lateral habenular nucleus;decreasing the content of NO,cGMP and th e expression of NR1,nNOS,iNOS,NR2A and NR2B mRNA in hippocampus samples,thus maintaining the balance of NO-cGMP signal pathway.