Rs-fMRI And Experimental Study On The Central Regulatory Mechanism Of Abdominal Vibration Therapy In The Treatment Of Dysmenorrhea Of Cold Stagnation And Blood Stasis Typ

Primary dysmenorrhea（PD）with cold,stasis,and pain as the main symptoms seriously affect the health of patients and their quality of life.It is attracting extensive attention from the medical community.Through high-frequency and low-amplitude tremors,the method of vibrating the abdomen affects the abdominal acupoints and meridians centered on the shenque,to invigorate Yin and reach Yang,relieving menstrual cramps.In the previous study,a series of theoretical and clinical projects have been declared around the abdominal vibration manipulation therapy,including the clinical optimization and promotion study of the method of vibrating the abdomen in the treatment of PD with cold coagulation and blood stasis and the literature study of internal organs manipulation with abdominal vibration therapy as the core.These studies proved the strengths of abdominal vibration manipulation therapy in treating internal and gynecological diseases,and initially established the effectiveness of the therapy in the treatment of PD with cold coagulation and blood stasis.To further ensure the accuracy and rigor of the study,this study refines the key technique of abdominal vibration manipulation therapy,the method of vibrating the abdomen,and further investigates the clinical efficacy and mechanism efficacy of the method of vibrating the abdomen in treating PD with cold coagulation and blood stasis.Modern medical research believes that the abdomen is the second brain of the human body,and the brain has almost the same kinds of substances as the abdomenrelated organs.Stimulating the abdomen centered on shenque through Tuina is able to regulate the neuroendocrine system,thus achieving the purpose of treating PD.Therefore,this study further investigates the antispasmodic analgesia by ventral abdominal vibration based on the relationship between the abdominal brain and the brain.And to investigate whether the method of vibrating the abdomen can affect the hypothalamic-pituitary-ovarian axis（HPOA）through regulating the central nervous system to affect the related indicators of the uterus,thus achieving the therapeutic effect of wenjing zhitong。Research objectives:To prove the clinical efficacy of the method of vibrating the abdomen in treating PD with cold coagulation and blood stasis.,and investigate the the antispasmodic analgesia by ventral abdominal vibration based on RS-FMRI technology.To investigate the mechanism of efficacy of abdominal vibration therapy in the treatment of PD with cold coagulation and blood stasis using HPOA as the regulatory axis.Research methods:1.Clinical observation on the treatment of primary dysmenorrhea with cold coagulation and blood stasis by abdominal vibration therapyIn study 1 of this dissertation,a small sample size clinical trial was conducted to observe the clinical efficacy of the abdominal vibration therapy in the treatment of PD patients with cold coagulation and blood stasis.20 patients were included in the abdominal vibration treatment.Except 5 patients failed to receive treatment regularly resulting in shedding,15 cases were determined to be valid data.The changes in VAS score,CMSS score,a total score of TCM syndrome,SAS score,SDS score,and PSQI indicators in PD patients with cold coagulation and blood stasis after treatment by abdominal vibration were observed.One-way ANOVA was then used to count the measures as well as the counts by chi-square test,by SPSS 19.0 software.2.Analysis of brain RS-FMRI detection of PD patients with cold coagulation and blood stasis by abdominal vibration therapyThe subjects recruited for this study are the same as those observed for the clinical efficacy of abdominal vibration in PD patients.Subjects underwent resting state functional magnetic resonance imaging（RS-FMRI）scans of the brain during menstrual cycle 0（baseline）and 3 days prior to menstrual cycle 1.The second scan was performed simultaneously with abdominal vibration therapy.Low frequency amplitude（ALFF）and functional connection（FC）analysis are data statistical analysis methods of RS-FMRI technology,which have been widely used in the research of various diseases.Therefore,RS-FMRI technology was used to observe FC changes before and after abdominal vibration treatment with differences between ALFF groups as seed points,and the correlation between VAS score and FC changes in the whole brain of PD patients with cold coagulation and blood stasis was analyzed to explore the central mechanism of immediate effect of abdominal vibration treatment in PD patients with cold coagulation and blood stasis.Two-sample T test was used to analyze the differences of ALFF and FC in PD patients with cold coagulation and blood stasis,and FWE（family-wise Error）correction was performed.3.Effect of abdominal vibration therapy on HPOA of cold coagulation and blood stasis dysmenorrhea model ratsIn study 2,30 female SD rats in diestrus were selected as the research objects,and 30 rats were divided into control group,model group and abdominal vibration group by random number table method,with 10 rats in each group.Estradiol benzoate was subcutaneously injected into the abdomen of the model group and the abdominal vibration group after freezer freezing to produce sensitivity to oxytocin,and the model was prepared by intraperitoneal injection of oxytocin combined with pain before observing behavior.After the success of the model preparation,abdominal group of the belly of vibration simulation of vibration meter timing quantitative simulation technique treatment,through the observation group rats body torsion reaction temperature,and the body surface projection of the uterus and cytology and molecular biology technology in detecting blood stasis type of dysmenorrhea haemorrheological nature GnRH in rat hypothalamus,HPOA key hormone and expression changes of uterine local index.Research results:1.Clinical results of abdominal vibration in the treatment of PD patients with cold coagulation and blood stasis1.1.VAS score resultsThere were significant differences before and after the first,second and third treatment（P<0.01）.There were significant differences after the first treatment and after the second treatment（P<0.05）,and after the third treatment（P<0.01）.There was no difference between the second and third treatments（P>0.05）.1.2.Results of total onset time of CMSSThere was a significant difference between before and after the first treatment（P<0.05）and after the second and third treatment（P<0.01）.There was no difference after the first treatment and the second treatment（P>0.05）,but there was no difference after the third treatment（P<0.05）.There was no difference between the second and third treatments（P>0.05）.1.3.Average severity of CMSSThere was a significant difference between before and after the first treatment（P<0.05）and after the second and third treatment（P<0.01）.There was a significant difference between the first treatment and the second and third treatment（P<0.05）.There was no difference between the second and third treatments（P>0.05）.1.4.Total score of TCM syndromesThere was a significant difference between before and after the first treatment（P<0.05）and after the second and third treatment（P<0.01）.There were significant differences after the first treatment and after the second treatment（P<0.05）,and after the third treatment（P<0.01）.There was no difference between the second and third treatments（P>0.05）.For the analysis of Pittsburgh Sleep Quality Index,Self-rating Anxiety Scale and Selfrating Depression Scale,the relevant data processing was not done because the subjects had no obvious sleep,anxiety and depression at the time of enrollment.2.Analysis of brain RS-FMRI of PD patients with cold coagulation and blood stasis by abdominal vibration methodThe rS-FMRI study was conducted on the premise that the abdominal vibration method had a definite clinical effect on PD patients with cold coagulation and blood stasis.2.1.ALFF analysis resultsAfter abdominal vibration treatment,there were inter-group differences in the right putamen,left insula and right cerebellar foot area 1 in PD patients,and the ALLF value increased.2.2.Results of FC analysis using the brain regions related to ALFF differences between groups before and after treatment as seed pointsAfter abdominal vibration treatment,FC in the right globus pallidus,thalamus,left insula and thalamus of PD patients was enhanced and positively activated,while FC in the right insula,left horn gyrus and middle frontal gyrus was weakened and negatively activated.2.3.Results of correlation analysis between VAS score and changes of global brain FC in PD patients with cold coagulation and blood stasis①VAS score of PD patients with cold coagulation and blood stasis was positively correlated with FC changes in the right insula（correlation coefficient>0,P<0.05）,and negatively correlated with FC changes in the right globus pallidus,left insula,left and right thalamus（correlation coefficient<0,P<0.05）.There was no significant correlation between VAS score and left angular gyrus and left middle frontal gyrus（P>0.05）.②There was a significant negative correlation between right insula and right globus pallidus,left insula,left thalamus and right thalamic FC（correlation coefficient<0,P<0.01）.③The changes of right globus pallidus and right thalamus were positively correlated with FC in left insula and left thalamus（correlation coefficient>0,P<0.01）.3.Results of the effect of abdominal vibration on HPOA of PD model rats with cold coagulation and blood stasis3.1.Comparison of torsional reaction and projection temperature of uterine surface in ratsThe latency of twisting body in model group was shorter than that in control group,the number of twisting body was more than that in control group,and the total score of twisting body was higher than that in control group.The torsional latency of the abdominal vibration group was longer than that of the model group,and the total torsional score was lower than that of the model group,with statistically significant differences（P<0.01）.The torsional times of the abdominal vibration group were less than that of the model group,with statistically significant differences（P<0.05）.The uterine surface projection temperature in model group was lower than that in control group.The projection temperature of uterine surface in abdominal vibration group was higher than that in model group,and the difference was statistically significant（P<0.05）.3.2.Results of expression levels of PGF_2α,PGE₂ and β-EP in rat serumThe expression levels of PGE₂ and β-EP in model group were lower than those in control group,and PGF_2α was higher than those in control group,with statistical significance（P<0.05）.The expression levels of PGE₂ and β-EP in abdominal vibration group were higher than that in model group,while PGF_2α was lower than that in model group,with statistical significance（P<0.05）.3.3.Results of expression levels of PGF_2α,PGE₂ and β-EP in rat uterus tissueCompared with the control group,the expression level of PGF_2α in uterus of model group increased,while the expression level of PGE₂ and β-EP decreased.Compared with model group,the expression level of PGF_2α in abdominal vibration group was decreased,and the expression level of PGE₂ and β-EP was increased,with statistical significance（P<0.05）.3.4.Results of the expression levels of FSH,LH and P values in serum of ratsCompared with the control group,the levels of serum sex hormones FSH and LH in model group increased significantly,but P value decreased.Compared with model group,the levels of serum sex hormones FSH and LH in abdominal vibration group were significantly decreased,and the P value was increased,with statistical significance（P<0.05）.3.5.Results of gnRH-R expression in pituitary and hypothalamus of ratsCompared with the control group,the expression of GnRH and GNRH-R in the hypothalamus of model group was significantly increased;Compared with model group,the expression of GnRH and GNRH-R in hypothalamus of abdominal vibration group was decreased,and the difference was statistically significant（P<0.05）.Research conclusions:1.The method of vibrating the abdomen has the effect of "wenjing zhitong",which can improve the symptoms of "cold","stasis" and "pain" in PD patients with cold coagulation and blood stasis.2.The central mechanism of the "spasmolysis and analgesia" effect of the method of vibrating the abdomen was related to the changes of the activity state of brain neurons in related brain regions.laying a foundation for exploring the analgesic mechanism centering on HPOA.3.The method of vibrating the abdomen can downregulate the expression of hypothalamic GnRH and related receptors,regulate the content of related hormones in HPOA,and then locally inhibit the production of PGF_2α in the uterus and upregulate the content of β-EP,playing the role of "wenjin zhitong".