摘要
【目的】
本课题为“十一五”国家科技支撑计划重大项目,通过研究补肾活血法对PD患者运动症状、中医证候、生活质量、脑神经递质DA水平、肌张力、运动并发症、美多芭用量等指标的影响,以达到优化PD中西医结合治疗方案,提高临床疗效,减轻西药副作用的目的。
【方法】
①采用多中心、随机、双盲、安慰剂对照方法,按标准纳入120例PD患者,其中治疗组60例和对照组60例。治疗组以补肾活血颗粒配合美多芭治疗,对照组单用美多芭治疗。前3个月为双盲观察,后6个月为揭盲后观察。在入组后及第1月、2月、3月、6月、9月后进行UPDRS, PDQ-39, PDSS,中医证候量化分级表,记时运动试验、十米折返运动试验和美多芭用量等的测量、评分与记录。对其中60例PD患者,在治疗前及治疗第1月、2月、3月、6月、9月后均采用EFG分析仪和Myotonometer(?)肌肉状态测试系统进行测量。
②采用多元线形广义回归统计分析方法,建立重复测量的线性拟合数据模型,分析“UPDRSⅡ”,“UPDRSⅢ”、“十米折返运动”、“记时运动”、“睡眠评分”等结局指标的影响因素。
【结果】
①治疗组(补肾活血组)的UPDRSⅢ,十米折返和记时运动等指标均较对照组有明显改善,在随访期内UPDRSⅢ和起立时间等具有显著性(P<0.01)。记时运动中治疗组可见双手运动次数增加,但组间比较无差异性(P>0.05)。UPDRSⅡ, PDSS和PDQ-39的认知力、情感、躯体不适等5个维度评分,在治疗过程中均有明显下降(P<0.05)。PDQ-39中社会支持、交往等维度无组间差异性(P>0.05)。治疗组中医证候积分显著改善(P<0.01),有效率达85.50%。
②治疗组DA总体水平呈上升趋势(P<0.05),对照组部分患者DA水平略微上升,但与治疗组比较无差异性(P>0.05)；治疗期内治疗组患者左侧肱二头肌和股四头肌静息肌张力改善有统计学意义(P<0.05),随访期内治疗组患者双侧肱二头肌和股四头肌静息肌张力均有改善(P<0.05),其中肱二头肌具有显著差异(P<0.01)。最大自主收缩状态时两组间比较均没有差异性(P>0.05)。
③治疗组食欲下降、睡眠障碍、症状位置性障碍等并发症改善显著(P<0.01),随着治疗时间增加,异动症和症状波动的评分也明显降低(P<0.05)。治疗组部分患者美多芭用量减少,主要分布在H-Y分级2～3级,对照组出现药量增加的情况。治疗终点时,治疗组出汗、便秘,排尿障碍的发生率显著低于对照组(P<0.01)。
④在本课题研究中,“UPDRSⅡ”、“UPDRSⅢ”、“起立时间”等指标的显著影响因素为“H-Y”(P<0.01)。“十米折返行走时间”的影响因素为“美多芭用量”、“H-Y”(P<0.05)。“睡眠评分”的影响因素为“美多芭用量”(P<0.05)。“左手记时试验”的影响因素为“年龄”(P<0.01)；“右手记时试验”的影响因素为“年龄”、“病程”(P<0.05)。
【结论】
①治疗组PD患者运动功能的改善率较对照组显著,且疗效稳定。治疗组PD患者的中医证候显著改善,有效率达85.50%。补肾活血法能明显改善PD患者日常生活能力和睡眠状况,并从认知力、情感、躯体不适等多方面提高生存质量。
②补肾活血法能显著提高PD患者脑内DA水平,并能在一定程度上缓解静息状态下肱二头肌和股四头肌肌张力增高的症状。
③补肾活血法可显著减少PD患者运动并发症(汗多、便秘、排尿障碍症状)的发生,减少美多芭用量,减轻美多芭的副作用。随着治疗时间的延长,补肾活血法“减毒增效”作用逐渐显现。
④在本课题研究中,PD患者“H-Y”、“美多芭用量”为“UPDRSⅡ”、“UPDRSⅢ”、“十米折返试验”、“睡眠评分”等疗效指标的共同影响因素。
[Objective]
To study the optimized scheme for treatment of Parkinson's disease(PD)with combined Traditional Chinese and Western medicine, which is supported by National Ministry of Science and Technology "Eleventh Five-Year" project. We adopted motor signs, symptoms in TCM, quality of Life, levels of DA in brain, muscular tension, usage of Madopar to observe the effects of Strengthening Kidney and Activating Circulation (SKAC).
[Method]
①A multi-center, randomized, placebo-controlled, double-blind clinical study was undertaken. Totally 120 PD patients were randomly divided into treatment group and placebo group, both groups based on Madopar treatment. All patients were treated for 9 months, including 6 months'follow-up period. The above-mentioned assessment scale, and symptoms in TCM, security indicators for drug adverse effects were measured at each time point:before treatment, treatment after 1,2,3,6,9 month. Among which,60 patients were enrolled in measurement of EFG and Myotonometer at the meantime.
②We established the multiple linear regression mode to analyze the effects of "sex", "age", "duration", "H-Y" and "Madopar" on "UPDRSⅡ", "UPDRS III", "10m x 2 time", "Ji-Shi-Test(JST)" and "Sleep" after analysis of repeated measurement data in the study.
【Result】
①arameters such as UPDRSIII score,10m×2 test and JST were ameliorated in treatment group at each time point. UPDRSIII score and time of getting up showed significant statistical difference in following-up period(P< 0.01).The times of left and right hands showed no statistical significant difference between groups(P>0.05);The scores of UPDRSⅡ, PDSS, and some aspects of PDQ-39 showed statistical significant in both treatment and following-up periods(P<0.05). Symptoms in TCM were improved markedly (effective power 85.50%).
②The treatment group showed a higher efficacy than the placebo group in increasing the levels of DA not only in treatment period (P<0.05), DA level in the placebo group was slightly increased, but no statistical difference was found between groups (P>0.05);The treatment group showed a higher efficacy in relieving motor function obstacle, from the aspects of both biceps brachii and quadriceps femoris (P<0.05), especially in biceps brachii (P<0.01).
③The symptoms of poor appetite, sleep disorders were significant statistical difference(P<0.01). With the extension of treatment time, the scores of dyskinesia and motor fluctuation was reduced(P<0.05).The usage of Madopar in treatment group were decreased, especially in patients with H-Y 2-3,but placebo group were increased; Treatment complications scores (Sweating,Constipation, Urination disorder) were reduced after 9 months,compared with placebo group(P <0.01).
④"H-Y" showed significant effects on "UPDRSⅡ", "UPDRSⅢ", "getting up time" (P<0.01), "Madopar" and "H-Y" had effects on "10m×2 time" (P <0.05), "Madopar" on "sleep" (P<0.05), "age" on "JST-left" (P<0.01) and "age", "duration" on "JST-right" (P<0.05).
【Conclusion】
①SKAC treatment can improve motor signs and symptoms in TCM of PD patients significantly(effective power 85.50%).The curative effects were more permanent and stable. From the aspects of Ability of Daily Life, Sleep Initiation &Maintenance Disorders and Psychophysiologic Disorders, quality of life of PD patients improved markedly in treatment group.
②Levels of DA in brain and static muscular tension were significantly improved with the effects of the SKAC treatment.
③Usage of Madopar and score of treatment complications in treatment group were decreased. SKAC treatment can decrease the side-effects of Madopar and put off the development of PD. The longer treatment time, the more significant effects of "Attenuation and Synergia" for SKAC.
④There is a correlation between "H-Y", "Madopar" and clinical evaluation indexes for PD treatment:"UPDRSⅡ", "UPDRSIII"," 10m×2 time" and "Sleep".
引文
[1]Gibb UR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease[J]. J Neurol Neurosurg Psychiatry.1988;51:745-752.
[2]Hughes AJ, Daniel SE, Lees AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease[J]. Neurology.2001;57(8):1497-1499.
[3]张颖,梁伟波,雒晓东.中药定振汤治疗帕金森病临床对照研究[J].辽宁中医杂志.2008；35(5)：728-729.
[4]路煜.熄风止颤汤联合美多芭治疗帕金森病临床研究[J].上海中医药杂志.2009；43(6)：20-22.
[5]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[6]窦永起,杨明会,刘毅,等.中西医结合治疗帕金森病疗效的对照观察[J].中国临床康复.2006；10(19)：6-8.
[7]胡良平.现代统计学与SAS应用[M].军事医学科学出版社.1996.
[8]“十一五”国家科技支撑计划相关文件[M].2007,p3.
[9]郑筱萸.中药新药临床研究指导原则(试行)[M].北京：中国医药科技出版社.1993：91-94.
[10]卞兆祥,李幼平,]Moher D,等.提高中草药随机对照试验的质量Ⅰ：临床试验设计和方法学[J].中西医结合学报.2006；4(2)：120-129.
[11]王海明.补肾活血法治疗帕金森病的作用机理研究[M].军医进修学院硕士学位论文,2007；p29.
[12]李军艳.赵冠英教授补肾活血法治疗帕金森病的临床研究[M].军医进修学院硕士学位论文,2009；p31-35.
[1]陈海渡,王新德译统一帕金森病评定量表(3.0版,1987)[J].中华老年医学杂志.1999；18：6.
[2]Mitchell S.Harper D, Lau A,et al.Patterns of outcome measurement in Parkinson's disease clinical trials[J].Neuroepidemiology.2000; 19(2):100-108.
[3]孙振球主编.医学统计学[M].人民卫生出版社.2002年第1版：P205-206.
[4].杨明会,李敏,窦永起.补肾活血法治疗帕金森病的理论探讨[J].中国中医基础医学杂 志.2009；15(11)：812-814.
[5]李军艳,杨明会,赵冠英.试论肾虚血瘀是帕金森病的基本病机[J].中华中医药杂志.2008；23(9)：768-771.
[6]张燕辉.运动功能检测对帕金森病早期诊断的意义[J].脑与神经疾病杂志.2005；13(2)：155-156.
[7]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[8]窦永起,杨明会,刘毅,等.中西医结合治疗帕金森病疗效的对照观察[J].中国临床康复.2006；10(19)：6-8.
[9]Fahn S.Adverse effects of levodopa.in:Olanow CW, Lieberman AN, eds.The scientific basis for the treatment of Parkinson's disease[J].Lancs,UK:Parthenon publishing Group.1992:89-112.
[10]尹伟华.左旋多巴诱导运动障碍和症状波动的临床和基础研究[M].苏州大学硕士学位论文,2003；9.
[11]张鸿,戴永萍,苏敏,等.重复经颅磁刺激治疗帕金森病的临床研究[J].临床神经病学杂志.2005；18(4)：266-269.
[12]赵澎,程焱,陶华英,等.帕金森病患者运动皮质兴奋性的经颅磁刺激研究[J].脑与神经疾病杂志.2006；14(2)：120-124.
[13]赵澎,程焱,陶华英,等.重复经颅磁刺激对帕金森病运动功能及运动诱发电位的影响[J].中国临床神经科学.2007；15(4)：397-401.
[1]Siderowf A, McDermott M, Kieburtz K, et al. Test-retest reliability of the unified Parkinson's disease rating scale in patients with early Parkinson's disease:results from a multicenter clinical trial [J]. Mov Disord,2002,17:758-763.
[2]PetoV,JenkinsonC,FitzpatrickR.PDQ-39:a review of the development, validation and application of a Parkinson's disease quality of life questionnaire and its associated measures[J].J Neurol,1998;245(Supp11):S10.
[3]Damiano AM,Snyder C,Strausser B,et al.A review of health-related quality-of-life concepts and measures for Parkinson's disease[J].Quai l,ife Res.1999;8:235.
[4]Jenkinson C, Fitzpatrick R, Peto V, et al. The Parkinson's Disease Questionnaire (PDQ-39):development and validation of a Parkinson's disease summary index score[J].Age Ageing.1997;26:353-357.
[5]Chaudhuri KR.Nocturnal symptom complex in PD and its management[J].Neurology.2003; 61(Supp 3):S17-S23.
[6]孙振球主编.医学统计学[M].人民卫生出版社.2002年第1版：p205-206.
[7]Hely MA,Morris JG,Reid WG,et al. Sydney Multieenter Study of Parkinson's disease non-L-dopa-responsive problems dominate at 15 years[J].MovDisorc.2005;20(2):190-199.
[8]尹伟华,刘春风,罗蔚峰,等.影响帕金森病患者生活质量因素的研究[J].临床神经病学杂志.2004；17(6)：446-447.
[9]董青,王智樱,李焰生.帕金森病患者健康相关生活质量的影响因素研究[J].中国神经精神疾病杂志.中国神经精神疾病杂志.2008；34(10)：598-600.
[10]吴逸雯,张干静,等.影响帕金森病患者生活质量的主要因素.临床神经病学杂志.2005；18(1)：16-18.
[11]Den Oudsten BL,Van Heck GL,De Vries J.Quality of life and related concepts in Parkinson's disease A systematic review[J].Mov Disord.2007;22(11):1528-1537.
[12]KUMAR R,LZANO AM,KIM Y I,et al.Double blind evaluation of sub thaiantic nucleus deep brain stimulation in advanced Parkinson's:disease[J]. Neurology.1998;51(3): 850.
[13]Den Oudsten BL,Van Heck GL,De Vries J.Quality of life and related concepts in Parkinson's disease A systematic review[J].Mov Disord.2007;22(11):1528-1537.
[14]Charles H,Adler, MD,et al. Nonmotor Complications in Parkinson's disease[J].Mov Disorders,2005,2o(11):s23-s29.
[15]Ferreira JJ, Desboeuf K, Galitzky I. Sleep disruption,daytime somnolence and'sleep attacks'in Parkinson's disease:a clinical survey in PD patients and age-matched healthy volunteers. [J] Eur J Neurol,2006,13(3):209-214.
[16]Comella CL. Slee disturbances and excessive daytime sleepiness in Parkinson's disease: an overview. [J] Neural Transm Suppl.2006,70:349-355.
[17]Pal PK,T hennarasu K,Fleming J,et al. Nocturnal sleep disturbances anddaytime dysfunc tion in patients with Parkinson's disease and in their caregivers[J].Parkinsonism Related Disords,2004;10(3):157-168.
[18]苏敏,刘春风,罗蔚峰.帕金森病睡眠障碍及影响因素研究[J].中国临床神经科学.2005；13(3)：279-282.
[19]Gagnon JF,Bedard MA,Fantini ML,Petit D,Panisset M,Rompre S,Carrier J,Montplaisir J.REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease[J]. Neurology.2002;59(4):585-9.
[20]Schenck CH,Bundlie SR,Ettinger MQet al. Chronic behavioral disorders of human REM sleep:a new category of parasomnia[J]. Sleep 2002;25(2):293-308.
[21]Factor SA,McAlamey T,Sanchez Ramos JR,et al.Sleep disorders and asleep effect in Parkinson's disease. Mov Disord 1990,4:280-285.
[22]Dzirasa K,Ribeiro S,Costa R,et al.Dopominergic control of sleep-wake states[J].J Neurosci,2006;26(41):10577-10589.
[23]Porter B,Macfarlane R,Walker R.The frequency and nature of sleep disorders in a community-based population of patients with Parkinson's disease[J].Eur J Neurol.2008,15(1): 50-54.
[24]Goetz CG,Wuu J,Curgian LM,et al.Hallucinations and sleep disorders in PD:six-year prospective longitudinal study [J].Neurology.2005;64(1):81-86.
[1]陈海渡,王新德译统一帕金森病评定量表(3.0版,1987)[J].中华老年医学杂志.1999；18：6.
[2]孙振球主编.医学统计学[M].人民卫生出版社.2002年第1版：p205-206.
[3]Fahn S.Adverse effects of levodopa.in:Olanow CW, Lieberman AN, eds.The scientific basis for the treatment of Parkinson's disease [J].Lancs, UK:Parthenon publishing Group.1992:89-112.
[4]尹伟华.左旋多巴诱导运动障碍和症状波动的临床和基础研究[M].苏州大学硕士学位论文.2003；p9.
[5]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[6]窦永起,杨明会,刘毅,等.中西医结合治疗帕金森病疗效的对照观察[J].中国临床康复.2006；10(19)：6-8.
[7]王海明.补肾活血法治疗帕金森病的作用机理研究[M].军医进修学院硕士学位论文.2007；p29.
[8]李军艳.赵冠英教授补肾活血法治疗帕金森病的临床研究[M].军医进修学院博士学位论文.2009；p31-35.
[9]陈生弟.中国帕金森病治疗指南(第二版)[J].中华神经科杂志.2009；42(5)：352-355
[10]E.K.Tan, S.Y.Lum, M.C.Wong.Restless legs syndrome in Parkinson's disease[J],Neuro--logical Sciences.2002;(196)33-36.
[11]Poewe W. Psychosis in Parkinson's disease[J]. Mov Disord.2003;18(Supp16):580-587.
[12]Marsh L.Neuropsy chiatricaspects of Parkinson's disease[J].Psychosomatics.2000;41(1): 15-23.
[13]Lewis SJ,Foltynie T, Blackwell AD, Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach[J]. J Neurol Neurosurg Psychiatry.2005;76(3):343-348.
[14]M.F. Siddiqui,S.Rast, M.J.Lynn et al. Autonomic dysfunction in Parkinson's Disease:a comprehensive symptom survey[J]. Parkinsonism and Related Disorders.2002;(8):277-284.
[1]郑筱萸.中药新药临床研究指导原则(试行)[M].北京：中国医药科技出版社.1993：91-94.
[2]陈呈祥整理.中医老年颤证诊断和疗效评定标准(试行)[J].北京中医学院学报.1992；15(4)：39-41.
[3]陈海渡,王新德译统一帕金森病评定量表(3.0版,1987)[J].中华老年医学杂志.1999；18：6.
[4]孙振球主编.医学统计学[M].人民卫生出版社.2002年第1版：p205-206.
[5]李军艳,杨明会,赵冠英.试论肾虚血瘀是帕金森病的基本病机[J].中华中医药杂志.2008；23(9)：768-771.
[6]杨明会,李敏,窦永起.补肾活血法治疗帕金森病的理论探讨[J].中国中医基础医学杂志.2009；15(11)：812-814.
[7]马龙.帕金森病分层治疗临床研究[M].北京中医药大学博士学位论文.2008；p55,66.
[8]杨明会,李军艳,刘毅.系统论引领帕金森病治疗思路[J].医学与哲学.2009；30(2)：3-5.
[9]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[10]窦永起,杨明会,刘毅,等.中西医结合治疗帕金森病疗效的对照观察[J].中国临床康复.2006；10(19)：6-8.
[1]Gibb UR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease[J]. J Neurol Neurosurg Psychiatry 1988;51:745-752.
[2]Hughes AJ, Daniel SE, Lees AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease[J]. Neurology.2001;57(8):1497-1499.
[3]“十一五”国家科技支撑计划相关文件[M].2007；p3.
[4]郑筱萸.中药新药临床研究指导原则(试行)[M].北京：中国医药科技出版社.1993：91-94.
[5]卞兆祥,李幼平,]Mloher D,等.提高中草药随机对照试验的质量Ⅰ：临床试验设计和方法学[J].中西医结合学报.2006；4(2)：120-129.
[6]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[7]窦永起,杨明会,刘毅,等.中西医结合治疗帕金森病疗效的对照观察[J].中国临床康复.2006；10(19)：6-8.
[8]王海明.补肾活血法治疗帕金森病的作用机理研究[M].军医进修学院硕士学位论文,2007；p29.
[9]李军艳.赵冠英教授补肾活血法治疗帕金森病的临床研究[M].军医进修学院博士学位论文,2009；p31-35.
[10]曾远明,李长清,胡长林.脑电超慢涨落图的正常参考值[J].现代医药卫生.2004；20(15)：15-22.
[11]Aarrestad DD,Williams MD,Fehrer S,et al.Intra-and inter-rater reliabilities of the Myotonometer for assessing the spastic condition of children with cerebral palsy [J] Journal of Child Neurology,2004;19(11):894-901.
[12]Charles T. Leonard PT, William P. Deshner,et al.Myotonometer Intra-and Interrater Reliabilities[J],Arch Phys Med Rehabil,2003;(84):928-932.
[13]CharlesT.Leonard Jason S.Brown,Timothy R.Price,Comparison of surface electromyography and myotonometric measurements during voluntary isometric contractions[J] Journal of Electromyography and Kinesiology.2004;(14):709-714.
[14]程英武,詹红生,元唯安,等.扌衮法对健康人腓肠肌肌张力影响的初步研究[J].上海中医药杂志,2007；41(7)：42-43.
[15]程英武,阴涛,詹红生,等.神经根型颈椎病斜方肌肌张力与推拿疗效相关性研究[J],天津中医药药.2008；25(7)299-301.
[16]孙振球主编.医学统计学[M].人民卫生出版社.2002年第1版：p205-206.
[17]Geer PL.Aging and extrapyamaidal function[J].Arch Neurol,1977;34:33.
[18]陈生弟,刘振国.帕金森病临床新技术[M].北京：人民军医出版社,2002,第1版：69,42-43.
[19]陈生弟,乐卫东,陈先文,等.帕金森病[M].北京：人民卫生出版.2006；第1版.73,138,41,446,265.
[20]Scherman D,Desnos C,Darchen F,et al.Striatal dopamine transporters with [123I] FP-CITSPECT dose not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease[J].Synapse,2001;39(2):101-108.
[21]Burn DJ,Troster AI.Neuropsychiatric complications of medical and surgical therapies for Parkinson's disease[J].J Geriatr Psych Neurol,2004;17:172-180.
[22]王丽敏,刘中霖,陶恩祥,等.帕金森病患者血浆单胺类神经递质的变化水平[J].中国临床康复,2005；9(5)：60-61.
[23]刘道宽,蒋雨平,江澄川,等.锥体外系疾病[M].上海：上海科学技术出版社.2000：73-74.
[24]张理义,徐志熊.ET在某些神经疾病中的应用综述[J].神经疾病与精神卫生,2006；6(1)：54-56.
[25]郭春荣,许维春,唐卫东,等.抑郁症患者脑电超慢涨落检测分析[J].临床精神医学杂志,2006,16(4)：226-227.
[26]梅磊.ET-脑功能研究新技术[M].北京：国防工业出版社.1995；288-300,356-362.
[27]韩艳,王振福,孙虹,等.帕金森病患者脑内神经递质变化的研究[J].中华保健医学杂志.2009；11[1]：24-26.
[28]李军艳,杨明会,赵冠英,等.应用脑电超慢涨落图技术对帕金森病患者脑内神经递质变化的研究[J].疑难病杂志.2009；8(1)：3-5.
[29]杨明会,窦永起,刘毅.抑颤汤对帕金森病模型大鼠行为学及脑黑质细胞形态学的作用.中国中西医结合杂志,2002,22(11)：841-843.
[30]窦永起,杨明会,王炜,刘毅.抑颤汤对帕金森病大鼠旋转行为、黑质细胞及神经递质的影响.中国临床康复.2003,7(28)：3832-3833.
[31]窦永起,杨明会,刘毅,王炜.抑颤汤对帕金森病模型大鼠旋转行为及M和DA受体的影响.中国医药学报,2003,18(11)：658-660.
[32]杨明会,王海明,刘毅,窦永起.抑颤汤对帕金森病大鼠脑内多巴胺受体和神经降压素含量的影响.中国中西医结合急救杂志,2008,15(2)：71-73.
[33]Siegfried Mense, David G. Simons, I. Jon Russell.肌痛[M].北京：人民卫生出版社,2005：85-86.
[34]李军艳,杨明会,赵冠英,试论肾虚血瘀是帕金森病的基本病机[J].中华中医药杂志.2008；23(9)：768-771.
[1]Gibb UR,Lees AJ.The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease[J].J Neurol Neurosurg Psychiatry 1988;51:745-752.
[2]Hughes AJ,Daniel SE,Lees AJ.Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease[J].Neurology.2001;57(8):1497-1499.
[3]张颖,梁伟波,雒晓东.中药定振汤治疗帕金森病临床对照研究[J].辽宁中医杂志.2008；35(5)：728-729.
[4]路煜.熄风止颤汤联合美多芭治疗帕金森病临床研究[J].上海中医药杂志.2009；43(6)：20-22.
[5]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[6]窦永起,杨明会,刘毅,等.中西医结合治疗帕金森病疗效的对照观察[J].中国临床康复.2006；10(19)：6-8.
[7]胡良平.现代统计学与SAS应用[M].军事医学科学出版社.1996.
[8]“十一五”国家科技支撑计划相关文件[M].2007；p3.
[9]郑筱萸.中药新药临床研究指导原则(试行)[M].北京：中国医药科技出版社.1993：91-94.
[10]卞兆祥,李幼平,]Moher D,等.提高中草药随机对照试验的质量Ⅰ：临床试验设计和方法学[J].中西医结合学报.2006,4(2)：120-129.
[11]王海明.补肾活血法治疗帕金森病的作用机理研究[M].军医进修学院硕士学位论文,2007；p29.
[12]李军艳.赵冠英教授补肾活血法治疗帕金森病的临床研究[M].军医进修学院硕士学位论文,2009；p31-35.
[13]张文彤等.SPSS统计分析高级教程[M].北京希望电子出版社.2002；06第一版：p337.
[1]陈清棠,余宗领.临床神经病学[M].北京：北京科学技术出版社.2001：382-383.
[2]王维治主编.神经病学第4版[M].北京：人民卫生出版社.2001：206-213.
[3]Pankratz N,Foroud T.Genetics of Parkinson disease[J]. NeuroRx.2004; 1:235-242.
[4]Poiymeropoulos MH,Lavedan C,Leruy E,et al.Mutation in the a-synuclein gene identified in families in the Parkinson's diseases[J].Science.1997;276(5321):2045-2047.
[5]Mouradian MM.Recent advances in the genetics and pathogenesis of Pakinson disease[J].Neurology.2002;58(2):179-185.
[6]Kawamoto Y,Akiguchi I,Nakamura S.Accumlation of 14-3-3 proteins in glial cytoplasmic inclusions in multiple system atrophy[J].Ann Neurol.2002.52(6):722-731.
[7]Shtilerman MD,Ding TT,Lansbury PT J,et al.Molecular crowding accelerates fibrillization of a-synuclein:could an increase in the cytoplas micprotein concentration Induce Parkinson's disease[J].Biochemistry.2002,;41:3855-3860.
[8]PetrucelliL,O'Farrell C,Lockhart P J,etal.Parkin protects against the toxicity associated with mutant a-synuclein:proteasome dysfunction selectively affects catecholaminergic neurons[J].Neuron.2002;36:1007-1019.
[9]Kitada T,Asakawa S,Hattori N,et al.Mutation in the parkin gene cause autosomal recessive juvenile parkinsonism[J].Nature.1998;392(6676):605-608.
[10]Shemlan MY,Goldberg AL.Cellular defenses against unfolded proteins:a cell biologist thinks about neurodegenerative diseases[J].Neuron.2001;29(1):15-32.
[11]Mcnaught KS,Olanow CW.Proteolytic stress:a unifying concept for the etiopathogenesis of Parkinson's disease[J].Ann Neurol.2003;53(suppl3):S73-84.
[12]Schlossmacher M G,Frosh M P,Gai W P,etal.Parkin Localizes to the lewy bodies of Parkinson's disease and Dementia with lewy bodies[J].Am J Pathol.2002;160:1655-1667.
[13]LiuY,Fallon L,Lashuel H A,etal.The UCHL1 Gene encode two opposing enzymatic activities that affect a-Synuclein degradation and Parkinson's disease susceptibility [J]. Cell. 2002; 111:209-218.
[14]Clark LN,Afridi S,Mejia-Santana H,et al.Analysis of an early-onset parkinson's disease cohort for DJ-1 mutations[J].Mov Disord.2004; 19:796-800.
[15]Yokoua T Sugawara K, Ito K, et aL.Down regulation of DJ-1 enhances cell death by oxidative stress,ER stress and protcasome inhibition[J].Biochcm Biophys Res Commun.2003; 312(4):1342-1348.
[16]Andres-Mateos E,Perier C Zhang L.DJ-1 gene delelion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase[J].Proc Natl Acad Sci USA.2007;104(37):14807-14812.
[17]Sctsuic R,Wang YL,Mochizuki H,et al.Dopaminergic neuronal loss in transgenic mice expressing the Parkinson's disease-associated UCH-L1 193 M mutants[J].Neurochem Int.2007;50(1):119-129.
[18]Polymeropeoulos H.Mutation in the a-synucleln and parinsons disease:selective neurodegenertive effect of a-synuclein fragment of dopaarninergie neurons in vitro and in vivo[J].Ann Neurol.2000;47(5):632-640.
[19]Forloni GBertani I.a-synuclein gene and Parkinson's disease selective neurodegenerative effect of a-synuelein fragment of dopaminergic neurons in vitro and in vivo[J].Ann Neural.2000;47(5):632-640.
[20]Damier P,Kasmer A.Does monoanine oxidase type B play a role in dopa miergic nerve cell death in parkinsons disease? [J].Neurology.1996;46(5):1262-1269.
[21]Mercuri NB,Fedrici M,Bernardi G.Inhibition of catechol-0 methyltransferase(COMT)in the brain not affect the action of dopamine and levodopa:an in vitro electrophysiological evidence from rat mesencephalic dopamine neurons[J].J Neura Fransm.1999;106(11,12):1135-1140.
[22]Homwit JM,Myers J.Identification and distribution of Parkin in ratbrain.Neuroreport. 1999;10(16):333-339.
[23]Langston J W,Ballard P A,Tetrud J W,et al.Chronic parkinsonism in humans due to a product of meperidine-analog synthesis[J].Science.1983;219:979-980.
[24]Tipton KF,Singer TP.Advances in our understanding of the Mechanisms of the neurotoxicity of MPTP and related compounds[J].J Neurochem.1993;61:1191-1206.
[25]Przedborski S,Jackson-Lewis V,Yokoyama R,et al.Role of The neuronal nitricoxide in MPTP induced dopaminergic neurotoxicity [J].Pro Nat Acad Sci USA.1996;93:4565-4571.
[26]赵永波,王乔树,郭春妮,等.一氧化氮合酶抑制剂对帕金森病模型大鼠神经损伤的影响[J].中华老年医学杂志,2004；23：414-417.
[27]Wang J,Xu Z,Fang H,et al.Gene expression profiling of MPP+ treated MN9D cells A mechanism of toxicity study[J].Neurotoxicology,2007;28(5):979-987.
[28]Perl DP,Olanow CW.The neuropathology of manganese-induced Parkinsonism[J].J Neuropathol Exp Neurol.2007;66(8):675-682.
[29]Mcmillan DE.Abrief history of the neuro behavioral toxicity of manganese:some unanswered questions[J].Neurotoxicology.1999;20:499-507.
[30]Seidler A,Hellenbrand W,Robra BP,et al.Possible environmental,occupational,and other etiologic factors for Parkinson's disease:a case-control study in Germany[J].Neurology.1996;、 46:1275-1284.
[31]Binolfi A,Rasia RM,Rasia RM,et al.Interaction ofa-Synuclein with divalent metal ions reveal skey differences:a link between structure,binding specificity and fibrillation enhancement[J]. J Am Chem Soc.2006;128:9893-9901.
[32]Duran E,Chacon JR.Parkinsonism probably induced by manganese [J].Rev Neurol.2001; 33:434-436.
[33]Gorell JM,Peterson EL,Rybicki BA,et al.Multiple risk Factors for Parkinson's disease[J].J Neurol Sci.2004;217:169-174.
[34]李国君,耿荣,褚金花,等.不同年龄大鼠对二价锰和三价锰致纹状体毒作用易感性的差异[J].卫生毒理学杂志.2004；18：326.
[35]Zheng W,Zhao Q,Slavkovich V,et al.Alteration of iron Homeostasis following Chronic exposure to exposure to Manganese in rats[J].Brain Res.1999;833:125-132.
[36]Zheng W,Zhao Q.Iron overload following manganese expose Incultured neuronal,but not neuroglial cells[J].Brain research.2001;897:175-179.
[37]卢玲,李国君,WeiZheng.锰干扰铁代谢致神经毒性的作用机制[J].国外医学卫生学分册.2002：29：170-173.
[38]陈先文,陈生弟,刘振国,等.铁剂诱发黑质多巴胺能神经元变性[J].中华老年医学杂志.2002：21：44-47.
[34]Betarbet R,Sherer TB,Maekenzine Qet al.chronic systemic pesticide exposure reproduces features of Parkinson's disease[J].Nat neurosci.2000;39(12):1301-1306.
[35]Shere TB.Subcutaneus rotenone exposure causes highly selective dopaminergic degeneration and synuclein aggregation[J].Exp Neurol.2003;179(1):9-16.
[36]Gomez C,Bandez MJ,Navarro A.Pesticides and impairment of mitochondrial functionin relation with the parkinsonian syndrome[J].Front Biosci.2007; 12:1079-1093.
[37]Ren Y,Liu W,Jiang H,et al.Selective vulnerability of dopaminergic neurons to microtubule depolymerization[J].J Biol Chem.2005;280(40):34105-34112.
[38]Radad K,Gille QRausch WD.Dopaminergic neurons are preferentially sensitive to long-term rotenone etoxicity in primary cellculture[J].Toxicol In Vitro.2008;22(1):68-74.
[39]Tsui J K,Calne D B,Wang Y,et al.Occupational risk factors in Parkinson's disease[J].Can J PH.1999;90:334-335.
[40]马莉,陈汶,高晓红,等.农业环境因素与帕金森病关系的病例对照研究[JJ.中国神经精神疾病杂志,2005,31：11-13.
[41]Thiruchelvam MEK,Richfield BM,Goodman RB,et al.Developmental exposure to the pesticides paraquat and maneb And the Parkinson's disease phenotype[J].Neuro Toxicol.2002;23:621-633.
[42]任今鹏,任惠民,蒋雨平.百草枯致帕金森病模型小鼠纹状体多巴胺D1、D2受体变化[J].中华老年医学杂志.2002：21：48-51.
[43]Semchuk KM,Love EJ.Effects of agricultural work and other prox3,derived case.control data on Parkinson's disease risk estimastes[J].Am J Epidemid.l995;141(8):747-754.
[44]陈荣杰,张本恕,王世民.帕金森病的性别差异及其原因探讨[J].天津医药,2009；37(3)：212-213.
[45]Baba Y.Putzke J.D.Whaley N.R.et al.Gender and the Parkinson's disease phenotype[J].世界核心医学期刊文摘.神经病学.2006；2(2)：32.
[46]Collier TJ,Lipton J,Daley BF,etal.Aging-Related Changes in the Nigrostriatal Dopamine System and the Response to MPTP in Nonhuman Primates:Diminished Compensatory Mechanisms as a Prelude to Parkinsonism[J].Neurobiol Dis.2007;26(1):56-65.
[47]Geer PL.Aging and extrapyamaidal function[J].Arch Neurol.1977;34:33.
[48]Booij J,Bergmans P,Winogrodzka A,et al.Imaging of dopam in transporters with [123I]FP-CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease [J].Synapse.2001;39(2):101-108.
[49]Irwin I,Delanney LE,McNeill T,et al.Aging and the nigrostrianta dopamine system:a non-human primate study[J].Neurodegeneration.1994;3(4):251-265.
[50]Nagayama H,Hamamoto M,Nito C, et al.Initial symptoms of Pakinson's disease with elderly onset[J].Gerontology.2000;46(3):129-132.
[51]Diederich N.I,Moore CG,Leurgans SE,et al.Parkinson disease with old-age onset a comparative study with subjects with middle age onset a comparative study with subjects with middle age onself[J].Arch Neurol.2003;60(4):529-533.
[52]Morens DM,Grandine A,Davis J W,et al.Evidence against the operation of selective mortality in explaining the associdtion between cigarette smoking and reduced occurceece of idiopathic Parkinson's disease[J].Am Jepidemiol.1996;144(489):400-404.
[53]Tanner CM,Goldman SM,Aston DA,et al.Smoking and Parkinson's disease[J].Brain Cogn.2000;43(856):274-276.
[54]Kelton MC,Kahn J,Conrath CL.et al.The effects of nicotine on Parkinson's disease[J].Brain,2002;58(964):581-588.
[55]Junn E,Mouradian MM.Apoptotic signaling in dopamine-induced cell death:the role of oxidative stress,p38mitogen-activated protein kinase,cytochrome c and caspases[J].Neuro-chem.2001;78(2):374-383.
[56]于战彩,李振光.以自由基学说探讨帕金森氏病的病因及治疗[J].生命的化学.1993；13(2)：26-28.
[57]Mawrin C, Kieches E, Kmuse G, et al. Region-specific analysis of mitochondrial DNA deletions in neurodegenrative disorders in humans[J].Neurosci Lett.2004;357:111-114.
[58]Antere J,Moilanen JS,Finnila S,et al. Mitochondrial DNA polymorphisms at risk factors:Parkinson's disease and Parkinson's disease dementia[J].Hum Genet.2004;115:29-35.
[59]Simon DK,Lin MT,Zheng L,et al. Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's disease[J].Neurobiol Aging.2004;25:71-81.
[60]Agid Y.Aging disease and nerve cell death[J].Bull Acad Natl Med.1995;179(6):1193-203.
[61]Rowe DB,Le WD,Smith RG,et al.Antibodies from patients with parkinson's disease react with protein modified by dopamine oxidation[J].J Neurosci Res.1998;53(7):551.
[62]邓建中,齐进兴,李玉岭,等.帕金森氏病患者免疫状态改变的研究[J].长冶医学院学报.2000；14(2)：107-108.
[63]irza B,Hadberg H,Thomsen P,et al.The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease[J].Neuroscience,.2000;95:425-432.
[64]iskum C, Starkov A, Polster BM, et al.Mitochondrial mechanisms of neural cell death and neuroprotective in terventions in Parkinson's disease[J].Ann N Y Acd Sci.2003;991:111--119.
[65]Macaya A,Munell F.Apoptosis in substantia nigra following developmental striatal excitotoxic injury[J].Proc Natl Acad Sci USA.1994;91:8117.
[66]McNaught KS,Olanow CW.Proteolytic stress a unifying concept for the etiopathogenesis of Parkinson's disease[J].Ann Neurol.2003;53(suppl 3):S73-S84.
[67]Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson's disease[J].Science.2003;302(5646):819-822.
[68]Ahlskog EJ. Slowing parkinson's disease progression Recent dopamime agonist trials[J].Neurology.2003;60(3):381-389.
[69]Fahn S,Oakes D,Shoulson I,et al.Levodopa and the progression of Parkinson's disease[J].N Engl J Med.2004;351:2498.
[70]Fahn S, A new look at levodopa based on the ELLDOPA study[J].J Neural Transm Suppl.2006;(70):419-426.
[71]Schwab RS,England AC,Poskanzer DC,et al.Amantadine in the treatment of Parkinson's disease[J].JAMA.1969;208:1168-1170.
[72]刘浩翔,刘玉玲,帕金森病治疗药物研究进展[J].中国药学杂志.2004；39(6)：409.
[73]邓安春,谭旭民.治疗帕金森的一线药物普拉克索[J].Foreign Medical Sciences Section on Pharnacy.2002;29(3):180.
[74]陈生弟,乐卫东,陈先文,等.帕金森病[M].第1版.北京：人民卫生出版社.2006；313,403.
[75]陈颖,左明新.帕金森病的常用药物治疗进展[J].首都医药.2006；9：40-41.
[76]葛关平.美多巴联合泰舒达治疗帕金森病临床观察[J].中国实用神经疾病杂志,2009；12(11)：73-74.
[77]Poewe W,Luessi F.Clinical studies with transdermal rotigotine in early Parkinson's disease.Neurology.2005;65(Suppll):S11-S14.
[78]FRUCHT S,ROGERS JD,GREENE PE,et al.Failing asleep at the wheel motor vehicle mishaps in persons taking pramipexole and ropinirole[J].Neurology.1999;52(9):1908-1910.
[79]The Swedish Parkinson Study Group. Selegiline slows the progression of the symptoms of Parkinson's disease[J].Neurology.2006;66(8):1200-1206.
[80]Parkinson Study Group.Effects of tocopheml progression of disability in early Parkinson's disease[J].N Engl J Med.1993;328:176.
[81]Keating GM,Perry CM.Spotlight on rasagiline in Parkinson's disease[J].CNS Drugs.2008;22(l)83-86.
[82]陈小朋,袁守军.帕金森病药物治疗的研究进展[J].国外医药.药学分册.2002；29(6)：351-354.
[83]孟慧,孙静慧.帕金森病的药物治疗[J].第四军医大学学报.2005；26(11)：1053-1054.
[84]Schrag A.Entacapone in the treatment of Parkinson's disease[J].Lancet Neuro.2005;4(6): 366-370.
[85]Chase TN,Bibbiani F,Bara-Jimenez W,et al. Translating A2A antagonist KW6002 from animal models to parkinsonian patients. [J].Neurology.2003;61(Suppl):S107-111.
[86]Mihara T,Mihara K,Yarimizu I,et al. Pharmacological characterization of a novel, potent adenosine Al and A2A receptor dual antagonist,5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), in models of Parkinson's disease and cognition. [J].J Pharmacol Exp Ther.2007;323(2):708-719.
[87]Weiss SM, Benwell K, Cliffe IA,et al. Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease. [J].Neurology.2003;61(Suppl): S101-106.
[88]CUNNING HAM LA,SUC.Astrocyte deliveru of glial cell line-derived nuerotrophic factor in amouse model of Parkinson's disease[J].Exp Neuro.2002;174(2):230-242.
[89]钱海燕.GDNF治疗帕金森病研究进展[J].立体定向和功能性神经外科杂志.2007；20(2)：116-118.
[90]OIWA Y.YOSHIMURA R,NAKAI K,et al.Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral,biochemical and histochemical measurementa in a model of progressive Parkinson's disease [J].Brain Res.2002;947(2):271-283.
[91]Thornel R G. Frey W.2nd Delivery of neurotrophic factors to the central nervous system phamacokinetic considerations[J].Clin Pharmacokinet.2001;40(12):907-946.
[92]刘泉开.帕金森病治疗的新进展[J].现代诊断与治疗.2000；(2)：65-67.
[93]张立湘,仝军.帕金森病的外科治疗近况[J].医学文选.2006；25(2)：346-347.
[94]刘承勇,漆松涛主编.帕金森病外科治疗[M].北京：人民卫生出版社.2004；第1版：105.
[95]王忠诚,张建国[J].中华神经外科杂志.2002；18(1)：1-3.
[96]刘彩霞.神经干细胞在帕金森病治疗中的研究进展.中风与神经疾病杂志.2007；24(2)：248-250.
[97]Siderowf A,Stern M.Update on Parkinson disease[J].Ann Intern Med.2003;138(8):651- 658.
[98]覃兰.帕金森病的治疗进展[J].医学文选.2005；24(4)：646-648.
[99]曲娟译.帕金森病的治疗[J].日本医学介绍.2005；26(10)：470-473.
[100]Lopez-Lozano JJ,Bravo G,Abascal J,et al.Clinical outcome of cotransplantatian of peripheral nerve and adrenal medulla in patients with Parkinson's disease[J].J Neurosurg.l999;90(5):875-882.
[101]Conti,Sip iones,Magrassi L.She signaling in eliferentia ting neural progenitor cells[J].Nature Neurosci.2001;4:579-586.
[102]Reynolds B A,Rietze R L,Neural stem cells and neurospheres reevaluating the relationship[J].Nat Methods.2005;2(5):333-336.
[103]Poll ak P,Fraix V,Kraek P,et al.Treatment Result:Parkinson's disease[J].Mov Disord. 2002;17(Suppl 3):S75-S83.
[104]刘承勇,漆松涛主编.帕金森病外科治疗[M].北京：人民卫生出版社.2004；360-336.
[105]史玉泉,周孝达主编.实用神经病学[M].第3版.上海科学技术出版社.2004；1047.
[106]陈彪,马敬红,邹海强.帕金森病基因治疗展望[J].中华神经科杂志.2005；38(6)：346-347.
[107]Moosmann B,Skutella T,Beyer K,et al.Protective activ ty of aromatic amines and imines against oxidative nerve cell death[J].Bio L Chem.2001;38(11):1601-1612.
[1]《黄帝内经·素问》[M].北京：人民卫生出版社.100,138.
[2]王文武,何建成.帕金森病的中医文献研究[J].新中医.2008；40(1)：118-120.
[3]孙一奎.赤水玄珠[M].北京：人民卫生出版社.1986；1125.
[4]王肯堂.证治准绳(一)[M].北京：人民卫生出版社.1991；435-437,578-580.
[5]白清林,古代中医对帕金森病的认识[J].北京中医药大学学报,2008,15(1)：34-35.
[6]老膺荣,朱泉.帕金森氏病中医思辨[J].辽宁中医杂志,2005,32(10)：1015-1016.
[7]隆呈样整理.中华全国中医学会老年医学会·中医老年颤证诊断和疗效评定标准[M].
[8]任继学,范国梁.震颤辨治[J].江苏中医.1982；4(4)：11.
[9]王永炎,蒋达树,侯力娜,等.中医药治疗震颤麻痹综合征35例疗效观察[J].中医杂志.1986；(8)：22.
[10]王永炎,李明富,戴锡孟,等.中医内科学[M].上海：上海科学技术出版社.1994；第6版：370.
[11]王克勤.震颤麻痹的中医治疗[J].中医药研究.1991；(2)：35-37.
[12]许继平.当代神经系统疾病的中医药治疗[M].济南：济南出版社.1994；第一：112-135.
[13]李军艳,杨明会,赵冠英.试论肾虚血瘀是帕金森病的基本病机[J].中华中医药杂志.2008；23(9)：768-771.
[14]杨明会,李军艳,刘毅.系统论引领帕金森病治疗思路[J].医学与哲学.2009；30(2)：3-5.
[15]王一德.帕金森综合征的中医辨治[J].安徽中医学院学报,1997,(3)：42-43.
[16]张连运,杨仕美.帕金森病的中医药治疗进展[J].山东中医杂志.2000；19(10)：637-639.
[17]廉全荣.帕金森病的中医辨证论治[J].河北中医.2006；28(1)：39-40.
[18]马龙.脾胃与帕金森病关系初探[J].天津中医药.2008；25(1)：37-39.
[19]武继涛.震颤麻痹从脾论治[J].浙江中医杂志.2003；38(9)：339.
[20]沈晓明.马云枝治疗帕金森病经验[J].中医杂志.2004；45(1)：14-15.
[21]朱红梅.震颤麻痹的病理探析[J].厦门大学学报自然科学版.2000；(64)：556-559.
[22]周仲瑛.读经典,谈感悟[J].南京中医药大学学报.2007；23(5)：273-277.
[23]宋秋云.帕金森综合征从痰从瘀论治[J].浙江中西医结合杂志.2004；14(11)：196.
[24]刘刚,刘昭纯.活血熄风法治疗帕金森病的理论与实验研究[J].山东中医药大学学报.2008；32(2)：136.
[25]王玲玲,何崇,刘跃光,等.帕金森氏病的情志调养[J].南京中医药大学学报.1997；13(4)：202.
[26]何建成.帕金森病中医药治疗的再思考-兼谈“滋肾平肝,化痰活血,解毒散结”是帕金森病的基本治疗法则[J].中医药通报.2005；4(1)：12-14.
[27]马启明,杜连平.中西医结合治疗帕金森病42例临床观察[J].中西医结合心脑血管病杂志.2003；1(10)：614.
[28]蔡定芳.帕金森病的中医治疗[J].中国现代神经疾病杂志.2009；9(3)：233-234.
[29]任继学,范国梁.震颤辨治[J].江苏中医.1982(4)：11.
[30]张保平,姜秀云,金杰.郑绍周.辨治震颤麻痹的经验[J].中国中医药学报.2003；18(4)：221.
[31]叶中峰.辨证分型治疗震颤麻痹36例[J].四川中医.2001；19(10)：30.
[32]章永红,章迅,赵镇兰.常见内科病中医治(二十四)[J].中国实用乡村医生杂志.2005；12(6)：11.
[33]周英豪.胡建华治疗震颤麻痹经验拾萃[J].上海中医药大学学报,2000,14(2)：20.
[34]刘泰.震颤麻痹病110例辨治规律探讨[J].辽宁中医杂志.2002；29(2)：82-83.
[35]李学文.中医辩证分型治疗震颤麻痹临床体会[J].包头医学.2000；24(3)：28.
[36]宋秋云.帕金森病中医证治体会[J].河南中医.2003；23(3)：471.
[37]国家食品药品监督管理局.国家基本药物(2004)[EB/OL].http://appl.sfda.gov.cn/web portal.2006-09-21.
[38]王刚,陈生弟.第五届全国帕金森病和运动障碍疾病学筋通络.对血虚瘀滞引起的肢体拘挛麻木有柔筋活术研讨会纪要[J].中华神经科杂志.2007；40(2)：142.
[39]张晓霞,吴之煌,冯耀辉.对帕金森病的病因病机与辨证治疗的认识[J].北京中医药.2008；27(9)：702-704.
[40]张军,张红梅,白丽敏,等.银杏平颤方及其拆方对MPTP模型小鼠脑内DA及其代谢产物含量的影响[J].中医药学报.2004；32(3)：12-14.
[41]安文.调气养神汤新用[J].河南中医.2001；21(4)：61-62.
[42]何永发.复元抗震汤治疗震颤麻痹18例[J].中国临床康复.2002；6(5)：747.
[43]葛邦雨.熄风定颤合剂治疗震颤麻痹33例疗效观察[J].河南中医.2003；23(4)：24-25.
[44]姚新.止颤胶囊治疗帕金森病的临床研究[J].吉林医学.2008；29(8)：653-654.
[45]景晓东,张海峰,郎丽辉.定颤丸治疗震颤麻痹34例[J].吉林中医药.2000；20(1)：38.
[46]鲍远程.抗震止痉Ⅰ号冲剂治疗帕金森病30例[J].中医杂志.2001；42(5)：312.
[47]郭淑睿,张彩玉,等.坎离丸治疗帕金森病19例[J].辽宁中医杂志.2001；28(3)：154-155.
[48]陈敏.补肾止颤汤治疗帕金森病临床观察[J].吉林中医药.2005；25(9)：12-13.
[49]谭文澜.帕金森病中医证型与病程各期关系探讨[J].湖北中医杂志.2005；27(9)：7-8.
[50]彦杰,李社宣.赵国华治疗帕金森病经验[J].光明中医.2002；19(4)：42.
[51]沈晓明.马云枝治疗帕金森病经验[J].中医杂志.2004；45(1)：14-15.
[52]张华,雒晓东.中医六经厥阴辨证治疗早中期帕金森病的临床研究[J].中医药学报.2008；36(6)：34-36.
[53]丰广魁,邵凤扬,等.中药镇颤舒治疗震颤麻痹的疗效分析[J].中国临床康复.2002；6(3)：334-335.
[54]王文同,雒晓东,吴薇,等.滋阴熄风活血汤治疗早期帕金森病20例临床观察[J].中医杂志.2004；45(4)：274-275.
[55]王亚丽.疏筋解毒汤治疗帕金森病临床研究[J].山东中医药大学学报.2009；33(1)：26-27.
[56]韩娟,鲍远程.中西医结合治疗帕金森病120例临床观察[J].中医药临床杂志.2004；16(3)：250-251.
[57]顾锡镇.西药加定颤饮治疗帕金森病30例临床观察[J].南京中医药大学学报·自然科学版.2002；18(5)：275-277.
[58]杨明会,窦永起,刘毅,等.抑颤汤治疗帕金森病临床对照观察[J].中国中西医结合急救杂志.2002；9(5)：256-257.
[59]王震宇.龟羚帕安丸治疗帕金森病38例[J].中医研究.2005；18(11)：37-38.
[60]胡学军,胥新元,肖波飞.中西医结合治疗对帕金森病患者生存质量及疗效的观察[J].中医药学刊.2004；22(4)：707-708.
[61]汤湘江.中西医结合治疗帕金森病的临床研究[J].四川中医.2006；(5)：44.
[62]王恩龙,王健,周鸿飞,等.养肝熄风中药治疗帕金森病临床研究[J].辽宁中医杂志.2008；35(2)：227-228.
[62]郜文,王丽娟,景朋,等.银杏叶提取物及银杏总内酯对帕金森病大鼠模型的作用[J].中国新药杂志.2000；9(7)：458-461.
[64]曹非,孙圣刚,曹学兵,等.银杏叶提取物防止帕金森病大鼠黑质细胞损伤的实验研究[J]. 中国老年学杂志.2002；22(3)：217-219.
[65]张林波,杨贵贞.三七皂甙Rg1纹状体内注射对帕金森病模型大鼠免疫炎症损伤的拮抗效应[J].中国免疫学杂志.2004；20(2)：121-123.
[66]郑鸿燕,曾水林,李涛.丹参注射液促帕金森病移植神经元存活的实验研究[J].江苏药学与临床研究.2004；12(2)：1-3.
[67]Byung-Soo Koo,Tae-Sig Kwon,Cheorl-Ho Kim.Salviae miltiorrhizae radix inhibits superoxide generation by activated rat microglias and mimics the action of amphetamine on in vitro rat striatal dopamine release[J]. Neurochemical research.2004;29(10):1837-1845.
[68]王丹巧,王巍,景富春,等.川芎嗪对左旋多巴处理的PD大鼠纹状体细胞外液DA及其代谢产物、羟自由基水平的影响[J].中国药学杂志.2007；42(1)：28-32.
[69]王丹巧,王巍,景富春,等.川芎嗪对帕金森病大鼠脑内灌流左旋多巴引起的脑氧化损伤的作用[J].中国中西医结合杂志.2007；27(7)：629-632.
[70]杨海东,姜宏,宋宁,等.人参皂苷Rg1对MPTP致帕金森病模型小鼠多巴胺能神经元保护作用研究[J].解放军药学学报.2007；23(1)：17-21.
[71]王莎莉,李英搏,王亚平.人参总皂苷在神经干细胞移植治疗帕金森病模型小鼠中的作用[J].中国临床康复.2006；10(41)：19-21.
[72]蒲小平,李晓蓉,李慧浓,等.肉苁蓉成分campneoside Ⅱ对神经毒素MPP+诱发细胞凋亡的保护作用[J].北京大学学报(医学版).2001；33(3)：217-220.
[73]袁崇刚,白桦,阳飞昆.首乌制剂对MPTP引起的小鼠帕金森病的防治[J].华东师范大学学报(自然科学版).2002；(9)：95-98.
[74]王丹巧,王巍,赵德忠.制首乌对脑内灌流6-羟基多巴胺所致大鼠纹状体细胞外液羟自由基升高的影响[J].中国中西医结合杂志.2006；26(3)：236-239.
[75]Shi Gui-Fang,An Li-Jia,Jiang Bo,etal.Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo[J].Neuroscience letters.2006;403(3):206-210.
[76]陈旭东,钟小明,余鸿.神经干细胞的增殖分化及当归对其影响[J].四川解剖学杂志.2007；15(2)：18-21.
[77]程晓馨,李丰桥,黄敏等.雷公藤氯内酯醇对帕金森病大鼠多巴胺神经元的保护作用[J].药学学报.2002；37(5)：339-342.
[78]Bing Xue,Jian Jiao,Lei Zhang,etal.Triptolide upregulates NGF synthesis in rat astrocyte cultures[J].Neurochemical research.2007;32(7):1113-1119.
[79]李雪莉,孙圣刚.葛根素对帕金森病保护作用的实验研究[J].脑与神经疾病杂志.2002；10(1)：7-9.
[80]Philipp Saiko,Akos Szakmary,Walter Jaeger,etal.Resveratrol and its analogs:Defense against cancer,coronary disease and neurodegenerative maladies or just a fad?[J]Mutation Research.2008;658(1-2):68-94.
[81]David Vauzour,Katerina Vafeiadou, Jeremy P.E. Spencer.Inhibition of the formation of the neurotoxin 5-S-cysteinyl-dopamine by polyphenols.Biochemical and biophysical research communications[J].2007;362(2):340-346.
[82]陈忻,张楠,邹海艳等.黄芩苷对MPTP帕金森病小鼠的保护作用[J].中国中西医结合杂志.2007；27(11)：1010-1012.
[83]Li FQ,Wang T,Pei Z,Liu B,Hong JS.Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons[J]. Journal of Neural Transmission.2005;112(3):331-347.
[84]徐瑰翎.天麻对帕金森病大鼠神经元保护及机制的研究[J].北京中医药大学硕士毕业论文,2007.
[85]袁红,刘平,许建阳,等.天麻对帕金森病模型大鼠行为学、生物化学的影响[J].武警医学,2008；19(3)：239-242.
[1]陈海渡,王新德译.统一帕金森病评定量表(3.0版,1987)[J].中华老年医学杂志.1999；18：6.
[2]Mitchell S.Harper D, Lau A,et al.Patterns of outcome measurement in Parkinson's disease clinical trials[J].Neuroepidemiology.2000;19(2):100-108.
[3]陈海渡,曾相豫,张文记.帕金森病运动功能评分量表及一致性和敏感性检验[J].卒中与神经疾病.2001；8(1)：1-4.
[4]Peto V, Jenkinson C, Fitzpatrick R, et al. The development and validation of a short measure of function and well being for individual with parkinson's disease[J].Qual Life Res.1995;4:241-248.
[5]Peto V,Jenkinson C,Fitzpatrick R.PDQ-39:a review of the development, validation and application of a parkinson's disease duality of life questionnaire and its associated measures[J]. J Neurol.1998;245(suppl.l):S10-14.
[6]Tang KL,Chi I, Ho SL,et al.Translation and validation of the standard Chinese Version of PDQ-39:a quality of life measure for patients with parkinson's disease[J]. Mov Disord.2002;17(5):1036-1040.
[7]ChaudhuriK R,Pal S,DiMarco A,et al.The Parkinson's disease sleep scale:a new instrumentfor assessing sleep and nocturnal disability in Parkinson's disease[J].J Neurol Neurosurg Psychiatry.2002;73:629-635.
[8]陈呈祥整理.中医老年颤证诊断和疗效评定标准(试行)[J].北京中医学院学报.1992；15(4)：39-41.
[9]Watts RL,Glart SL,KolIer WC,Paulson Geds.Objective measures of motor diability In:Therapy of Parkinson's disease[J]. New York:Marcel Dekker.1990;31.
[10]Lang AE,KolIerWC,Paulson G eds.Clinical rating scales and videotape analysis In:Therapy of Parkinson's disease[J].New York MarceDekker.1990;3.
[11]张理义,徐志熊.ET在某些神经疾病中的应用综述[J].神经疾病与精神卫生.2006；6(1)：54-56.
[12]郭春荣,许维春,唐卫东,等.抑郁症患者脑电超慢涨落检测分析[J].临床精神医学杂志.2006；16(4)：226-227.
[13]李军艳,杨明会,赵冠英,等.应用脑电超慢涨落图技术对帕金森病患者脑内神经递质变化的研究[J].疑难病杂志.2009；8(1)：3-5.
[14]Marinus J, Visser M, Stiggelbout AM. A short scale for the assessment of motor impairments and disabilities in Parkinson's disease:The SPES/SCOPA[J].J Neurol Neurosurg Psychiatry.2004;75(3):388-95.
[15]中华全国中医学会老年医学会.中医老年颤证诊断和疗效评定标准(试行)[J].北京中医学院学报.1992；15(4)：39.
[16]陈海波,曾湘豫,张文记,等.帕金森病运动功能评分量表的一致性和敏感性检验及其优越性体现[J].中国临床康复.2004；8(4)：762-763.
[17]陈海波,曾相豫,张文记,等.帕金森病运动功能评分量表及一致性和敏感性检验[J].卒 中与神经疾病.2001；8(1)：1-4.
[18]刘凤斌,赵利.建立中医疗效测评量表体系研究的设想[J].中国临床康复.2004；8(1)：164-165.
[19]刘凤斌,方积乾,王建华.中医药临床疗效评价的探讨[J].中药新药与临床药理.2004；15(4)：290-292.
[20]赵虹,李文伟,高俊鹏,等.补肾养肝方药治疗肝肾阴虚型帕金森病临床研究[J].中国中西医结合杂志.2007；27(9)：780-784.
[21]谭文澜.帕金森病中医证型与病程各期关系探讨[J].湖北中医杂志.2005；27(9)：7-8.
[22]刘垣,陈彪.帕金森病患者中医证候调查[J].中医杂志.2009；50(8)：728-747.
[23]陈婉珉.帕金森病中医证候要素及证型分布规律的研究[M].广州中医药大学硕士学位论文.2009；p26-27.
[24]赖世隆.中医药临床疗效评价若干关键环节的思考[J].广州中医药大学学报.2002；19(4)：245-250.
[25]郭新峰,朱泉,赖世隆.替代指标和中间指标及其在中医药疗效评价研究中应用价值的思考[J].中国中西医结合杂志.2005；25(7)：585-590.
[26]余瑾,刘凤斌.帕金森病的生存质量研究和中医药疗效评价[J].中国康复理论与实践.2006；12(7)：641-642.
[27]马龙.帕金森病分层治疗临床研究[M].北京中医药大学博士论文.2009；p55.
[28]李军艳,杨明会帕金森病的中医药治疗[J].北京中医药.2008；27(4)：300-302.