【作者】 吴凌云；

【导师】 靳瑞；

【作者基本信息】 广州中医药大学 ， 针灸推拿学， 2006， 博士

【摘要】 帕金森病是一种常见的中老年人神经系统变性疾病,具有高发病率、高致残率的特点。有资料显示,50岁以上的发病率为500/10万人口,60岁以上则明显增加,为1000/10万人口。帕金森病在发病的10到15年内可以导致老年病人明显的残障。随着社会人口的老龄化,帕金森病的发病率正逐年增高,且有年轻化的趋势。帕金森病是继脑血管病之后,中老年人最为常见的一种病症,它严重的危害中老年人的身体健康和生活质量,给社会和家庭造成巨大的经济负担和精神压力。 作为21世纪神经科学重要的研究疾病之一,帕金森病(PD)目前尚无办法根治,且早期诊断率较低,各种客观诊断和检测指标还在研究当中、尚不成熟。当前PD治疗的目的主要在于控制临床症状,尽可能的维持病人独立的生活能力和良好的生活质量。尽管通过药物为主的内科治疗,在一定程度上可以有效地使PD患者控制病情、缓解症状和延缓病程,但是长期用药后,患者容易出现各种毒副作用和并发症,如剂末现象、开关现象、不自主的异动症、恶心、呕吐等,导致很多病人最后无法坚持治疗。为了减小西药毒副作用、增强临床疗效,目前人们越来越重视中医和针灸的治疗方法。临床资料显示针灸在治疗PD方面是行之有效的一种方法,但是目前国内外在此方面的研究却相对较少。 导师靳瑞教授所创立的“颤三针”疗法是在几十年治疗脑病的临床基础上总结而出的,它是以“四神针”为主的一组穴位,在临床治疗帕金森病中已经应用多年,且临床疗效显著。已有的工作基础表明运用“颤三针”治疗帕金森病具有明显的止颤作用,在减轻患者的临床症状、减少西药的毒副作用和并发症方面具有独特的效果。本课题就是在此基础上提出并进行研究的。 本文系统研究了针灸、中医及现代医学文献对帕金森病(老年颤证)的认识和研究进展,对颤三针治疗帕金森病从临床和实验两方面进行了研究。 目的:通过随机对照的临床研究方法,客观评价颤三针疗法对帕金森病(PD)的疗效;同时利用动物PD模型,初步探讨“颤三针”疗法治疗帕金森病(PD)的机理,进一步验证“靳三针”疗法在治疗脑病方面的科学性和实用性。 内容:本研究采用多学科先进研究方法和观察指标,对应用颤三针疗法治疗帕金森病的疗效和作用机理进行系统的前瞻性研究。在严格按照临床研究设计的基础上,对符合纳入标准的PD患者进行临床观察,通过目前世界公认的UPDRS评分法,计算病人治疗前后的各项相关积分,来观察应用颤三针疗法治疗PD患者的疗效。为临床寻找一种较安全有效而副作用小的临床治疗方法,提高PD患者的生活质量,降低这一高发疑难疾病的致残率,进一步验证“靳三针”疗法治疗脑病的疗效及其作用机制。 方法:临床研究,参照1984年全国锥体外系疾病讨论会所定的帕金森病(PD)诊更多还原

【Abstract】 Parkinson’s disease has become one kind of nervous system denatured disease in middle-aged and old people commonly, and it has the characteristic of high disease incidence and high crippling rate. Some data display that it has a disease incidence of 500 per 100 thousand population in age more than 50 years , and 1000 per 100 thousand population in age more than 60 years which increases obviously. The parkinson’ s disease can induce obvious handicap when old people get sick in 10 to 15 years. Following social population aging, the disease incidence of parkinson is advancing year by year, and also has a tendency of juvenescence. Parkinson’s disease is the most common disease in middle-aged and old people besides the cerebrovascular disease at present, which does harm to health and quality of life in middle-aged and old people seriously, bringing a huge economical burden and stress for society and family.As one of important researching diseases of neuroscience in the 21st century, parkinson’s disease(PD) still did not have the means to be radical cured at present, and the pristine diagnose rate is very low, various kinds of objective diagnosis and the detected index are to be researched, which are still not mature. The medicative goal of PD mainly lies in controlling clinical symptom, maintaining patient’ s independent viability and good quality of life as far as possible at present. Although through the medical treatment mainly in drugs can make the PD patient’s condition to be controlled effectively , relieving symptom and delaying course in the certain degree, but after long-term medication, the patients are easy to appear various kinds of toxical side effect and complication, e. g. dosage telophase phenomenon, switch-open phenomenon and heteronomous abnormal motion, nausea, vomito and so on, in the end many patients are unable to persist in treating. In order to reduce toxicalside effect of western medicine and enhance clinical curative effect, at present people more and more think highly of the treatment with Chinese medicine and the therapy of acupuncture and moxibustion. The clinical data demonstrated that acupuncture and moxibustion was a effective method in treating PD disease, but now relative researches are actually few in this aspect domestic and abroad.Tutor Pro. Jinrui established a therapy of "trembling-three needles" to treat PD disease, which based on the clinical foundation of treating cerebral disease in several dozens years, and it is a group of acupoints primary in "mind-four needles" , being already used many years in the clinical treatment for parkinson’ s disease, also it had a striking curative effect in clinic. The work foundation indicated that the therapy of "trembling-three needles" had a obvious function to stop tremble in treating parkinson’s disease, and it had a distinct effect in reducing patient’s clinical symptom, lessening toxical side effect of western medicine and complication. This topic was proposed and studied from the foundation.This article had studied the literature of acupuncture and moxibustion, Chinese medicine and modern medicine in cognition and research progress systematically to parkinson’ s disease (old people trembling), undertaking the clinical and experimental study on treating parkinson’s disease with trembling-three needles.Objective: Through the clinical research method at random and comparison, evaluating the curative effect of trembling-three needles to treat parkinson’ s disease (PD) objectively-, at the same time using the animals model of PD, discussing the mechanism preliminary on the therapy of "trembling-three needles" to treat parkinson’s disease (PD), further confirming scientific nature and usability about the therapy of "Jin-three needles" to treat the cerebral disease.Contents: This research used multidisciplinary advanced methods and observed index to carry out a systematic and prospective study on the curative effect and the mechanism of action which used therapy of trembling-three needles to treat parkinson disease. According to foundation of the clinical research designed strictly, carrying on the clinical observation of PD patients which are in line with the standard of internalization, through the UPDRS integration accepted universally at present, calculating patient’ s eachcorrelation integral of pretherapy and post-treatment, observing the curative effect of utilizing therapy of trembling-three needles to treat PD patients. For seeking one kind of safely-effective clinical method and diminishing the side effect, improving the PD patient’ s quality of life, reducing the crippling rate of this high incidence and difficult disease, in order to confirm the the curative effect and its functional mechanism of Jin-three needles therapy in treating cerebral disease.Methods: The clinical research, refering to the diagnostic criteria of parkinson disease(PD) which instituted in 1984 by the conference of extracorticospinal tract diseases, choosing 68 parkinsons patients which consistent with the diagnose and internalized standard, according to Hoehn and Yahr revised stage and divided patient’ s condition into light degree, midrange, heavy degree (0 to 1. 5 stage is light degree;2 to 3 stage is midrange;fourth, fifth stage is heavy degree), making manufacture stochastic cards, according to the laminar-stochastic method we divide the patients into trembling-three needles group for 35 cases, control group (taking medicine of Madopar primary) for 33 cases, two groups were all maintained the fundamental treatment with western medicine. The main acupoints of the trembling-three needles group was: Trembling-three needles (mind-four needles, siguan points and fengchi);Siguan acupoints were hegu and taichong bilateralis. Dialectical acupoints: yin-deficiency of Liver and kidney can add ganshu, shenshu and sanyinjiao;phlegm and heat lead to wind can add f englong, zhongwan, yinlingquan;insufficiency of vital energy and blood can add qihai, xuehai, zusanli. symptomatic acupoints: agrypnia patients can add dingshen needles, shouzhi needles;costive patients can add intestine-three needles;depressed people can add wisdom-three needles;nocturia patients can add yang-three needles. Every time of the acupuncture is 60 minutes, manipulating needle every 20 minutes, needling one time every other day, and a course of treatment is 15 times, observing two course of treatment continuously. In control group patients took medicine Madopar and so on, the dosage was decided by patient’ s condition and individual difference. Observed index.- evaluating the unified parkinson’ s disease rating scale (UPDRS), according to UPDRS we calculated the progressive rate of depression, sleep disorder, tremble inactivity, posture barrier, muscular rigidity, language and deglutation after the treatment. We carried on evaluating them separately during pretherapy and post-treatment,then carried out statistical analysis for testing results.Experimental study: The models of PD were established through the method of two points injecting 6-hydroxydopa(6-OHDA). Choosing 46 healthy male SD-rats in SPF level, among the total was experimental group for 30 rats, Physiological saline control group for 8, normal blank control group for 8. In the end it was 27 rats succeed in PD model after inducing by APO, so we divided them into three groups at random: model group for 9, western medicine treatment group (intragastric administration by Madopar) for 9, acupuncture treatment group for 9. Handling measurement: In normal blank control group, only grasping rats with hands but did not given any treament to them;in model group and physiological saline control group we made them recovery by themselves, in western medicine treatment group we given intragastric administration by Madopar to the rats (dosage of 240mg per kilogram, equivalent 7 times to the people’s concentration), one time everyday;in acupuncture treatment group we choosed baihui, hegu and taichong bilateralis to treat them, their allocation refered to the acupoints of rats. Treatment methods: Using number 30 and 1 cun length stainless steel acupuncture needle prick into baihui point deep in 0. 5 cun sparallelled, pricking into hegu and taichong point deep in 0. 5 cun perpendicularly, using the chirismus of rolling and extract-insert method, acupuncture treatment one time everyday, staying needle 30 minutes each time, manipulating needle one time per 5 minutes. The time of therapy of each group are all 2 months, when the time of therapy had completed we would take out of 2 rats from each group to make the pathological section at random and to make the morphology observation. At the same time we decapitated to kill the surplus rats, taking out left side of the cerebral nigra to detect activity of superoxide dismutase(SOD) and nitrogen monoxidum(NO), comparing the results of each groups and carrying on statistics analysis.Results:Clinical research: 1. Before treatment, trembling-three needles group and control group did not have statistics difference (P>0. 05) in total UPDRS score, and each part of grades for I, II, III, IV, so they had comparability. After treatment trembling-three needles group can reduce total UPDRS score and each part of grades remarkably (P<0.01), control group also improve total UPDRS score, I, II, III, IV parts (P<0.05);curative effect of trembling-three needles group was surpassed obviously to control group on treating parkinsondisease (P<0.05). It showed that the therapy of "trembling-three needles" had a remarkable effect to improve the motor symptoms of PD, enhancing the quality of life, eliminate complication of western medicine, moreover this kind of curative effect prominently lay in improving patient’s emotion and daily life ability. After treatment two groups had a remarkable enhancement in progresses rate (P<0.01);compared with control group, trembling-three needles group had a extremely remarkable difference in improving depression, dyssomnia, static tremorthe, language and deglutition (P<0.01);also it had a obvious effect to improve clinical symptoms e. g. motion, posture barrier and myotonia (P<0. 05). It explained trembling-three needles group had a good effect to stop tremble, and had a extremely remarkable effect to depression, sleeping, speaking and deglutation in PD patients, which was superior to the motor function improved. Experimental study: in model group dopamine(DA) neuron solidified, analosis, apoptosis massive;in acupuncture and the western medicine group can cause the DA neuron increasing massive, but western medicine group had a obvious superiority, this possible because of the acupuncture time was too short. In normal blank control group and physiological saline group neuron did not be changed. Acupuncture treatment group and western medicine treatment group can elevated SOD and reduce the NO activity obviously, displaying acupuncture and western medicine treatment can increase the ability of antioxidase in rats, eliminating free radical;SOD and NO contents can droped obviously in model group, it showed that the method of 6-OHDA chemistry damaging can cause the nigral dopamine neuron denatured death massively,-Acupuncture treatment can improve PD rats clinical symptoms enormously, and had suppresses a function to restrain neuron apoptosis.Conclusion: l.The study discovered the therapy of "trembling-three needles" can enhance the PD patient’s motor function remarkably, improving their daily life ability, alleviating complication of western medicine treatment effectively, and also this kind of curative effect mainly in relieving pressure of spirit and emotion, improving the function of autonomic nerve. 2. Experimental study discovered acupuncture can restrain DA neuron apoptosis effectively, increasing DA neuron quantity obviously, protecting the nigral neuron from denatured necrosis. 3. Acupuncture can strengthen SOD activity remarkably and reduce NO vigor, increasing the anti- oxidized ability, protecting PDrats brain from attacking and damage by the oxygen free radical.Trembling-three needles is one of essence in the therapy "Jin-three needles" , as a experienced-effective point which my tutor summarized when he had treated parkinson disease in clinic for many years, and it had accurate curative effect to treat parkinson disease. Using trembling-three needles to treat parkinson disease can improve the emotion behavior of patients obviously, and enhance the quality of life, reduce the medicine treatment complication, also have a remarkable curative effect of stopping trembles. Moreover the therapy had a good function to treating and adjusting the motor symptoms and three accessory symptoms (constipation, nocturia and agrypnia) of PD, also it had a very good treatment and control action to depression, sleeping, walking, writing, debilitation, aches, anxious and so on. This conclusion appraised curative effect of acupuncture treatment in PD by the objective angle for the first time, the effect of acupuncture treatment mainly in improving symptoms, delaying the course of disease, raising the patient’ s quality of life, reducing western medicine amount and the side effect, enhancing constitution and disease-resistant ability. Because acupuncture had a bilateral accommodation function to the human body, it did not have the obvious side effect, so it can be long-term used. For this reason, we believed acupuncture treatment had certain curative effect to PD, and it was a positive method to treat and rehabil PD. Experimental study results indicated that trembling-three needles therapy had a reliable curative effects, it is safe, non-toxic side effect, being worthy to generalization in clinical practice. Experimental study demonstrated trembling-three needles can achieve a therapeutic action as western medicine, the acupuncture’ s function was possibly to strengthen the anti-oxidized ability, clear free radical, depress DA neuron apoptosis, these mechanism may be play a role to treat PD.This experiment had proven that Jin-three needles therapy had special effect in treating cerebral disease from many systems and many angles, establishment of trembling-three needles therapy was a abundance and development for "Jin-three needles" therapy.更多还原