| Objective1.Animal model of phase induced migraine rats was induced by dopamine and nitr oglycerin.The model could be a scientific method to explore the regulation mechanis m of the method of harmonizing ying and wei in regulating cerebral blood flow and vasc ular endothelial function of phase induced migraine rats.And our research aimed at a nalyzing the best application dose of gui zhi(Ramulus Cinnamomi)and bki shao(Radix Paeoni ae Alba).2.Through the analysis of the headache attack situation and the TCM syndromes i n patients with migraine,and the analysis of the indicators in the PRO scale,our rese arch carried out the discussion on the feasibility of the clinical application of the meth od of harmonizing ying and wei,which will provide ideas for the prevention and treatme nt of migraine with traditional Chinese medicine,moreover,provide evidences for furt her clinical application.Method1.Replication of the rat model of phase induced migraine30 male SD rats were randomly divided into 3 groups,including blank group,solvent group and model group,10 rats in each group;the blank group without drug intervention.For the model group,subcutaneous injection of dopamine hydrochloride(20mg/kg)by weight,after 45min,abdominal subcutaneous injection of glyceryl trinitrate(10mg/kg);for the solvent group,subcutaneous injection of normal saline(0.2ml/100g)at the same point.Through the laser speckle blood flow perfusion video system(PeriCam PSI),dynamic observation of rat brain perfusion blood flow.After recording the cerebral perfusion blood flow after 9?18?27?36?45min and 1?10?19?28?37?46?55?64?73min administration.A total of 15 points administration in 2 hours.2.The optimal dose and the best compatibility proportion of gui zhi(Ramulus Cinnamomi)and bdi shoo(Radix Paeoniae Alba)on prevention and treatment of migraine2.1 Grouping,model making and observation of cerebral perfusion blood flowAccording to different dose and proportion,100 male SD rats were randomly divided into 10 groups,including blank group,gui zhi:bai shao(0g:Og)group,gui zhi:bai shao(0g:10g)group,gui zhi:bai shao(0g:20g)group,gui zhi:bai shao(10g:0g)group,gui zh i:bai shao(10g:10g)group,gui zhi:bai shao(10g:20g)group,gui zhi:bai shao(20g:0g)group,gui zhi:bdi shao(20g:10g)group,gui zhi:bai shao(20g:20g)group.Each group of 10 rats.The blank group did not establish a migraine model,the rest of the group established a migraine model.For each group of the migraine model group,they have 7 days of continuous administration of the corresponding drugs.The blank group did not fill the stomach.Observation of cerebral blood flow in SD rats after 7 days,the monitoring method was also same as characterized by the phase characteristic of the rat model of migraine.2.2 Monitoring of the content of neuropeptide in arterial bloodAbdominal aortic blood was taken 2 hours after modeling,determination of plasma ET levels by radioimmunoassay,determination of plasma NO content by spectrophotometry.3.A preliminary study on the clinical therapeutic effect of the treatment of migraine by the method of harmonizing the ying and weiPatients who meet the inclusion criteria were recruited into the group through outpatient clinics.After entering the group,the treatment was carried out by means of reconciliation of ying and wei.The course of treatment was 4 weeks,patients who stopped the medicine 4 weeks need to be followed up 1 times.Main outcome measures were the number of headache attacks,headache days,degree of headache;the secondary efficacy observation index were frequency of headache attack by half rate,the number of days of headache attack by half rate,the changes of TCM syndrome of Toufeng disease,the outcome evaluation'Which based on the report of migraine patients(PRO scale)and so on.Result1.Replication of the rat model of phase induced migraineIn the model group,the cerebral perfusion blood flow change rate,after the injection of dopamine hydrochloride at different 5 points,were statistical difference when compared with the blank group and solvent group.The cerebral tissue perfusion after injection of dopamine hydrochloride in migraine model rats was significantly decreased;in the model group,the cerebral blood flow perfusion changes after the injection of nitroglycerin at 1,10,19,28 min were significant difference in rate compared with the blank control group and solvent group,at the point of 37,46,55,64,73min,compared with the blank group,it was statistical difference,and the cerebral tissue perfusion of rats after injection of nitroglycerin was significantly increased.2.The optimal dose and the best compatibility proportion of(Ramulus Cinnamomi)and bai shao(Radix Paeoniae Alba)on prevention and treatment of migraine 2.1 Within group comparison of the model groups of migraine rats2.1.1 Comparison of cerebral perfusion and blood flow in rats with migraineIn migraine vascular contraction phase at the point of 9,18,27,45min,the change rate of cerebral perfusion blood flow in the rats of each migraine model group was statistical differences.Effect of gui zhiwas statistically difference at the point of 9,18min among different dose groups;bai shoo was statistically difference between each dose group at the point of 9,27,36,45min.The interaction between gui zhiand bai shao at different time points were statistically different.In contraction phase,the cerebral perfusion blood flow of the gui zhi:bai shao(10g:10g)group and the gui zhi:bai shao(20g:20g)group decreased at least.In migraine diastolic blood vessels phase,the change rate of cerebral perfusion b1 ood flow in each model group was statistically significant at different time points in d iastolic phase;gui zhi of different doses was statistically significant at the point of 1,10,19,28,55,64min.The interaction between gui zhiand bai shao at different time points in the blood vessels diastolic phase were statistically different.The cerebral perfusion blood flow rate of the gui zhi:bai shao(10g:10g)group and the gui zhi:bai shao(20g:20g)was the most obvious in rats.2.1.2 Comparison of the neuropeptide in the rat model of migraineThere were significant differences in ET-1 content between the groups of migraine model rats.The interaction between gui zhiand bai shao at different doses of gui zhi between different groups were statistically different.When the dosage of gui zhi:bai shao is 0g:20g,the content of ET-1 is lower,while the dosage of gui zhi:bai shao is 0g:0g,the content of ET-1 is the highest and the dosage of gui zhi:bai shao is 0g:10g,the content of ET-1 is the lowest.The NO content of each migraine model group was compared between groups,there was no significant difference in differnet doses of groups.2.2 Comparison between the blank group and migraine model group2.2.1 The difference of cerebral perfusion blood flow between the blank group and each migraine modelThe rate of change of cerebral perfusion blood flow rate in the blank group and the migraine model group was statistically different at each time point in the systolic phase.The gui zhi:bai shoo(20g:20g)group and the blank group had no significant difference at the point of 27,36min.No significant differences between the blank group and the group of gui zhi(10g)at the point of 18,27,45min;at each point of the diastolic phase,the difference was statistically significant.The gui zhi:bdi shao(20g:20g)group and the blank group in the diastolic phase at each time point compared with no significant difference;except the time point of 64min,there is no significant differences between the gui zhi:bai shao(10g:10g)group and the blank group.2.2.2 The neuropeptide difference between the blank group and the migraine groupThere was no significant difference in the content of NO in the blank group compared with the model group.The content of ET-1 in the blank group was statistically significant compared with the migraine model group.No statistically significant difference were found between the blank group,gui zhi:bai shao(20g:20g)group,gui zhi:b6i shao(20g:10g)group and gui zhi:bai shao(20g:Og)group.3.A preliminary study on the clinical therapeutic effect of the treatment of migraine by the method of harmonizing the ying and weiAfter 4 weeks of treatment,there was a significant difference in the frequency of headache attack,the degree of headache compared with the groups before treatment;the syndrome of Toufeng score and total score were improved,there was a significant difference between depression syndrome score compared with the groups before treatment;migraine PRO scale was compared with the groups before treatment,headache,somatic symptoms and PRO total score were statistically significant differences than the groups before treatmentConclusion1.Through the dopamine and nitroglycerin induction,we can successfully replicate the model of migraine rats with,vascular contraction phase and the phase of vascular expansion.2.Phase of migraine model rats with migraine attack,the regulation effect of the method of regulating the ying and wei has a regulatory effect on the blood flow of cerebral perfusion and the content of the artery in migraine rats.The gui zhi:bai shao(20g:20g)group can better maintenance the cerebral perfusion and blood flow in rats with migraine and decrease peripheral blood ET-1 by modulating the neuropeptide,which can effectively improve the vascular contraction of migraine rats.In general,the group of gui zhi:bai shao(20g:20g)and the 1:1 ratio are the optimal dose proportion in prevention and treatment of migraine.3.The method of reconciling ying and wei can improve the basic condition and TCM syndromes of migraine patients,there is therapeutic significance in treatment of headache attack and somatic symptoms.It is feasible in the prevention and treatment of migraine. |
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