| 1 The Background,Objectives and Significance of the ResearchVascular dementia(VD)refers to a clinical syndrome that manifests itself mainly in senior nerve cognitive dysfunction.It develops from the damage to the brain tissue induced by ischemic,hemorrhagic,acute or chronic ischemic-hemorrhagic cerebrovascular diseases. Compared with other kinds of dementia,VD has a better prognosis and more therapies,and can be prevented to some extent.However,modern medicine still doesn't have a therapy that can really ameliorate the whole course of VD nor any medicine that can effectively cure or completely prevent VD.In this respect,acupuncture therapy of VD has some unique advantages of its own owing to its two-way adjustment to abnormal nerve functions as well as specificity and entirety.The modeling of VD has long been a hindrance to the study of VD for the reason that it is difficult to establish and repeat such a model.Even there are models of this kind, they usually fail to reflect the essential pathogenesis of VD.What's more,most VD models made recently do not have corresponding Syndrome patterns described in traditional Chinese medicine,thus affecting the reliability of VD study in TCM.Despite that acupuncture therapy has some positive curative effects,there is still little effective and in-depth research on relative specificity of acupoints and hardly any prescription of composed acupoints.With all VD related to the vascular factor,it pathogenesis is described as that functional disorders of the cardiac-cerebral vascular system and microcirculation disturbance induce secondary hypoperfusion and ischemic damage to the brain tissues,thus resulting in dementia.However,dementia models established by executing cerebral ischemia and reperfusion to healthy rats are not consistent with the clinical pathogenesis of the disease.The mentor of the author-Lai XinSheng was the first to copy models of VD combined with hypertension.With regard to hazardous causative factors of VD,the production of these models simulates the development of VD.Besides,pathological changes produced by the models are much more similar to those clinically observed. However,compared with other risk factors,as VD induced by hypertension can reflect only a single aspect of the development of VD,there is still a gap between it and the clinic symptoms.Thus,VD induced by hypertension still has to be ameliorated.Hyperlipemia is usually accompanied by hypertension.Clinical studies on it indicate that hypertension and hyperlipemia are not only the most risky factors in the development of VD,but also mutually influence each other by raising the incidence rate and the severity of cerebro-vascular diseases and aggravating the progressiveness of dementia.For these reasons,in the present research we copied VD animal models combined with hypertension and hyperlipemia(hypertension-hyperlipemia vascular dementi,HH-VD)according to the pathogenesis of VD induced by multiple clinical factors.Furthermore,to investigate characteristics of the syndromes in TCM of these models,previous findings of the correlation between hypertension and kidney deficiency were taken into consideration together with the correlation between hyperlipemia-stagnant phlegmIn recent years,treatment of VD with acupuncture has achieved some remarkable curative effects that are well accepted by researchers in this field.There have been many comprehensive studies on this subject in both clinical and laboratory experiments with some accomplishments ranging from clinical to mechanism research.Professer Lai XinSheng,in his long investigations,has put forward an acupuncture prescription with Du 20(Baihui)and Du 14(Dazhui)as the main acupoints and has made some progress in the protection and restoration of the rats cranial neurons,antioxidase system and ameliorating cerebral blood flow.Based on these investigations,review and meta-analysis of relevant literature,we optimized the aforementioned prescription,it is named "Dredge Governing Meridian,adjust spirit and strengthen the congenital foundation".We established a hypertension-hyperlipemia vascular dementia model and experimented on acupunctural interference with it according to the optimized prescription.HAP axis/blood fat was selected as quantified index of the research as it not only reflects kidney deficiency and stagnant phlegm in TCM,but is also closely related to dementia.During the experiment,the daily behaviors,cerebral and nephridial tissue pathology of the rats were observed closely as part of the ethological tests.Accordingly, further research on the pathogenesis of VD was conducted and the new model was compared with the previous ones to make sure that it was physiologically and pathologically mature,objective and scientific and that it has the characteristics of kidney deficiency-stagnant phlegm syndrome described in TCM.In this research,the new model was interfered with by the optimized acupunctural prescription,whose results were compared with that of conventional western therapy and other acupunctural prescriptions. With the observation of the related index above,the therapeutic mechanism from the following two aspects was investigated,namely dredging Governing Meridian and adjusting the spirit to improve intelligence;strengthening the congenital foundation to refresh kidney and remove phlegm.Furthermore,the therapeutic effects were also investigated to confirm the peculiarity and advantages of the optimized prescription and thus provide strong evidence for its clinical application.2 MethodThe research can be divided into two parts,including literature study and experiments.In the literature study,by integrating ancient literature with current reports and documents,we summarized the knowledge and research achievements in vascular dementia in both traditional Chinese medicine and modem medicine.Moreover,we compared and evaluated the experimental animal VD models and carried out Meta analysis of the acupoint selection of the prescriptions of acupuncture treatment of VD in the past 10 years.The regularity of acupoint selection was investigated for optimized acupuncture prescription accordingly.The animals were randomized into HH-VD group,hypertension VD group, 4-VO group,2-VO group.The procedure of establishing the model is as follows:first, two-kidney one-clipped(2K1C)method was adopted to copy hypertension models;then, they were fed with high fat food to copy hypertension-hyperlipemia models;lastly,the modified two-vessel occlusion(2VO)method was applied to create ischemia in the rats' brain,which was followed by resumed perfusion,thus eventually resulting in dementia.In this way,a vascular dementia accompanied by hypertension-hyperlipemia model was copied.The optimized acupunctural prescription was applied to the interference study,the model rats were randomized into four groups.They are "dredge Governing Meridian,adjust spirit and strengthen congenital foundation" Electro acupuncture group,"dredge Governing Meridian,adjust spirit " Electro acupuncture group,non-acupuncture treating group and western medicine group.In the experiment,methods such as radio-immunity, histomorphology and ethological tests were used to investigate the pathogenesis of VD and the mechanism of electro acupuncture as well.Statistical method.Interclass analysis adopted multiple comparison of analysis of variance and Dunnett's C method was applied for heterogeneity of variance.T-test was applied to compare independent-samples.The data is denoted with mean±standard deviation((?)±s)and calculated with SPSS 13.0 for Windows. 3 Results3.1 The optimized acupuncture prescriptionBy Meta analyzing and summarizing the regularity of the prescriptions of acupuncture treating VD in the past ten years,we lay the optimized acupuncture prescription -- "dredge Governing Meridian,adjust spirit and strengthen congenital foundation" Electro acupuncture with the following acupoints:Du 20(Baihui),Du 20(Dazhui),GB 23 (Shenshu)and GB 20(Pishu).Further more,treating the VD models prepared by international received four-vessel occlusion(4-VO)method proves that the optimized prescription can regulate the secretion of cerebral neuropeptide and endothelin of VD rats, lessen the damage of the cranial nerves,and increase their abilities of learning and memory.3.2 Establishing a hypertension-hyperlipemia vascular dementia modelCompared with the hypertension VD model,models prepared with two-vessel occlusion(2-VO)method and four-vessel occlusion(4-VO)method,the new model is characterized by the following traits:1)the performance of ethological tests is much worse; 2)the damage to the brain and kidney is more severe,especially the small vessel lesion of the brain;3)they are accompanied by persistent hypertension and hyperlipemia;4)daily behaviors demonstrate kidney deficiency as well as HPA axis hypofunction,indicating that the new models has the characteristics of kidney deficiency-stagnant phlegm syndrome as described in TCM.3.3 The initial study of the optimized acupuncture prescription intervening in the new modelsThe optimized electro acupuncture prescription "Dredge Governing Meridian,adjust spirit and strengthen the congenital foundation" electro acupuncture can regulate the HPA function,increase model rats' abilities of learning and memory,without any significant deviation with the western medicine group.Moreover,the prescription can increase the amount and activity of the neural synapse in model rat's hippocampus,improve the symptoms of kidney deficiency-stagnant phlegm in model rats,and lessen the damage of target organs—brain and kidney.The effect of lessening the damage of target organs surpasses western medicine group and the "Dredge Governing Meridian,adjust spirit and strengthen the congenital foundation" electro acupuncture group as well as the non-acupuncture treating group.4 Conclusion and prospectFrom the above description and discussion,and our research in particular,we may safely draw a conclusion as follows:(1)It is feasible to establish a combined VD model on the basis of hypertension combined with hyperlipemia using two-vessel occlusion method.The combined model thus established demonstrates dementia accompanied by chronic hypertension and hyperlipemia before and after the cerebral ischemia,which is extremely similar to the pathogenesis of most VD patients clinically observed.The symptoms of the new model manifest HPA axis hypofunction,abnormal composition of the blood fat as well as mictufition.These symptoms are in line with the characteristics of kidney deficiency-stagnant phlegm syndrome described in TCM.(2)The optimized prescription "Dredge Governing Meridian,adjust spirit and strengthen the congenital foundation" electro acupuncture can up-regulate the HPS axis, cerebral neuropeptide and endothelin to lessen the damage to cerebral nerves from cerebral ischemia,activate hippocampus synapses,increase the amount and activity and improve VD rats' performance in water maze and Y maze tests.Besides,the prescription can not only improve the VD rats' learning ability and memory,but can also significantly alleviate some symptoms of kidney deficiency-stagnant phlegm syndrome in the VD rats.Overall,as a simultaneous treatment of principal and subordinate symptoms,it can improve the quality of their life.This effect outperforms the western medicine group and the "Dredge Governing Meridian,adjust spirit and strengthen the congenital foundation" electro acupuncture group,indicative of the advantages of the holistic therapy concept of TCM.Prospectively,further research following this is expected to integrate with the study of the mechanism of the damage to cerebral vessels from hypertension and hyperlipemia. Besides,the pathogenesis of VD and the mechanism of the validity of acupuncture will be looked into from the perspective of the relation between changes in the cerebral micro-vessels and small vessels and neuron damages as well as nerve regeneration. Moreover,through prescription separation,comparison and combination,the research on the specificity of each acupoint in the optimized acupuncture prescription and the results of their combination will provide evidence and support for further clinical application. Clinical research can integrate with the advantages of multiple therapies of TCM and establish a positive and comprehensive system integrating theory,method,prescription,and medicine to improve the clinical therapeutic effects.
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