医学交流课件：帕金森病中西医结合诊疗研究现状与展望

1、帕金森病中西医结合诊疗研究现状与展望帕金森病中西医结合诊疗研究现状与展望 Clinical Overview and Research Prospects of Parkinsons disease in the Integrative Chinese and Western Medicine 帕金森病（帕金森病（PDPD）: :又称震颤麻痹。是一种原因不明的、慢性进 行性加重的中枢神经系统变性性疾病。 ( Parkinsons disease (PD), also called paralysis agitans, is a chronic, progressive degenerative

2、 disorder of the central nervous system of unknown causes). 临床上以锥体外系运动障碍为特征，表现为运动徐缓、静止性 震颤和强直,此外病人还可出现吞咽困难，自主神经功能障碍 和痴呆。 (Clinically it is characterized by the motor symptoms of extrapyramidal system, manifesting as slowness of movement, static tremor and rigidity. Patient with PD also displays dysp

3、hagia, autonomic dysfunction and dementia). 图图1 PD患病率与年龄、地区的相关性研究患病率与年龄、地区的相关性研究 Movement disorders, 2014, 29: 1583-1590 PD 在65 岁以上西方人群中的患病率约0.1% 0.25%； 在中国患病率约1.7%。 临床特征：以锥体外系运动障碍为主，表现为运动徐缓、静止性震 颤和强直；还可出现吞咽困难，自主神经功能障碍和痴呆。 (Clinically it is characterized by the motor symptoms of extrapyramidal syste

4、m, manifesting as slowness of movement, static tremor and rigidity. Patient with PD also displays dysphagia, autonomic dysfunction and dementia). 图图2 PD运动症状（左）和非运动症状（右）运动症状（左）和非运动症状（右） Nature review, 2017, 18: 435-450 其特征性病理改变是中脑黑质多巴胺神经元的缺失 ，以及黑质神经元内出现Lewy小体。 (Its characteristic pathological changes

5、 include the death of dopaminergic neurons in the substantia nigra, a region of the midbrain and the appearance of Lewy body in residual neurons of substantia nigra). 图图3 PD的病理特征的病理特征 Nature review, 2017, 18: 251-259 图图4 PD200年研究的编年史年研究的编年史-I 缩写：ALS：肌萎缩性脊髓侧索硬化症； Nature review, 2017, 18: 251-259 图图5

6、PD200年研究的编年史年研究的编年史-II GBA：葡溏苷酰鞘氨醇酶；LAG3：淋巴细胞激活基因3；L-DOPA：左旋多巴； MPTP：1-甲级-4-苯基-1,2,5,6-四羟基吡啶；SNCA：-突触核蛋白 （一）病因与发病因素：（一）病因与发病因素：帕金森病帕金森病(PD)为第二大神经退行性为第二大神经退行性 疾病，疾病，大多数大多数PD 患者呈散发性，其中约患者呈散发性，其中约10% 15% 的患的患 者有家族史者有家族史；其发病可能与遗传、环境、年龄老化、免疫炎；其发病可能与遗传、环境、年龄老化、免疫炎 症、细胞凋亡、线粒体功能障碍等诸多因素有关。一般认为症、细胞凋亡、线粒体功能障碍等

7、诸多因素有关。一般认为 ，本病的发生是遗传与环境因素相互作用的结果。，本病的发生是遗传与环境因素相互作用的结果。 （Pathogenesis and pathogenic factors： PD is one of most common age- related neurodegenerative disease. The morbidity rate among people over 60 years old is 1%-2%. Its onset may be connected to many factors, such as heredity, environment, aging

8、, immune inflammation, apotosis, mitochondrial dysfunction and so on. It is generally acknowledged that it is the consequence of interaction of gene and environmental factors）. （二）分子流行病学研究：（二）分子流行病学研究：研究发现与帕金森病发病有关的基因已达研究发现与帕金森病发病有关的基因已达2121个。个。 Fig.1 Simplified workflows for whole-exome, whole-geno

9、me and transcriptome sequencing Ref: Nature Reviews Neuroscience, 2012, 13:453-464. Fig.2 Schematic overview of effect sizes and frequencies of genetic variants in PD genes identified by GWAS Ref: Molecular and Cellular Probes, 2016, 30: 386-396. Gene (locus)MethodologyClinical phenotype VPS35 Exome

10、 sequencing Typical, late-onset PD SYT11, ACMSD, STK39, MCCC1/ LAMP3; GAK, BST1, SNCA, HLA-DRB5, LRRK2, CCDC62/HIP1R, MAPT GWAS Familial or sporadic PD PARK16, STBD1, GPNMB, FGF20, STX1B GWAS Unknown SCARB2, SREBF1/RAI1 GWASEarly-onset and late-onset PD TNK2, TNRWESFamilial PD GWAS: genome-wide asso

11、ciation studies Table 1 Confirmed genes implicated in monogenic PD Ref: Nature Reviews Neuroscience, 2012, 13:453-464. Ann. Transl. Med., 2014;2(12):125. JAMA Neurology, 2016;73(1):68-75 Gene (locus)MethodologyClinical phenotype CEL, MPHOSPH10, TAS2R19, SERPINA1 WES/GWAS Early-onset PD GPATCH2L, UHR

12、F1BP1L, PTPRH, ARSB, and VPS13C WESSporadic PD DNAJC6WES Juvenile onset, atypical PD SYNJ1 Exome sequencing Juvenile onset, atypical PD EIF4G1WES GPATCH2L, UHRF1BP1L, PTPRH, ARSB, VPS13C WESFamilial PD WES: Whole-exome sequencing Table 1 Confirmed genes implicated in monogenic PD (continued) Ref: Ne

13、urobiology of Aging, 2017, 195: e7-e10. Genome Biology, 2017, 18: 22. Parkinsonism and Related Disorders, 2014, S23S28 其中最重要的为其中最重要的为PARK1PARK1基因突变基因突变： (Molecular epidemiology research：Nine genes related to PD have been found. Some popular genes see as follows): a-a-突触核蛋白突触核蛋白(a-(a-synucleinsynucle

14、in) )定位于定位于4q214q21-23-23，为，为PARK1PARK1基因突基因突 变变，是脑内一种突触前蛋白，与，是脑内一种突触前蛋白，与家族性早发帕金森病家族性早发帕金森病密切相密切相 关，是关，是散发性帕金森病散发性帕金森病和其他神经退行性病变中路易小体的和其他神经退行性病变中路易小体的 主要成分。主要成分。 (a (a-synuclein positioned on 4q21-23 is the genetic mutation of PARK1. It is a presynaptic protein existing in brain, closely related to

15、 familial early- onset PD, witch is the major component of Lewy body in sporadic PD and other neurodegenerative diseases). （三）分子病理学研究：（三）分子病理学研究：构象病是当代医学发展具有里程碑意构象病是当代医学发展具有里程碑意 义的分子医学新概念，为诸多重大疑难疾病由传统的姑息性义的分子医学新概念，为诸多重大疑难疾病由传统的姑息性 治疗向根治性治疗转变带来了突破的新希望。构象病即是由治疗向根治性治疗转变带来了突破的新希望。构象病即是由 分子构象异常的错误折叠蛋白质积聚

16、导致的一类疾病，错误分子构象异常的错误折叠蛋白质积聚导致的一类疾病，错误 折叠蛋白质积聚导致折叠蛋白质积聚导致ERSERS相关细胞凋亡是蛋白质构象病的核相关细胞凋亡是蛋白质构象病的核 心分子病理机制。心分子病理机制。 (New concept in Molecular pathology: Conformational disease, a new concept in molecular medicine, is a landmark in the development of modern medicine. It brings breakthrough and new hope to m

17、any gravely difficult diseases from traditional palliative treatment to radical treatment. Conformational disease is a kind of disease resulted from accumulation of misfolded abnormal molecular conformation proteins. Accumulation of misfolded proteins results in the apoptosis of ERS, which is the co

18、re of molecular pathological mechanism. Recently, many researches show that PD is a typical neurodegenerative conformational disease, and dysfunction accumulation and degradation of misfolded - synuclein is the key step in PDs pathogenesis) 图图6 PD信号转导相互作用通路图信号转导相互作用通路图 Cell Signaling Technology, 201

19、2 Neuron, 2016, 90: 675-691 图图7 PD中中-突触核蛋白聚集及纤维化突触核蛋白聚集及纤维化 （四）肠道菌群与（四）肠道菌群与PDPD：近期近期CellCell一项颠覆性研究成果一项颠覆性研究成果 发现肠道菌群失调是发现肠道菌群失调是PDPD的罪魁祸首，为的罪魁祸首，为PDPD的防治开辟了全的防治开辟了全 新的方向。新的方向。 研究识别到十几个属的肠道微生物可能介导研究识别到十几个属的肠道微生物可能介导PDPD发生；肠道微生物失调发生；肠道微生物失调 可能导致可能导致-synsyn错误折叠、通过脑肠轴影响包括中枢神经、自主神错误折叠、通过脑肠轴影响包括中枢神经、自主神

20、 经及肠道周围神经在内的各级神经功能，并与经及肠道周围神经在内的各级神经功能，并与PDPD患者非运动症状和运患者非运动症状和运 动症状密切相关动症状密切相关. . 图图8 脑脑-肠肠-微生物对话与微生物对话与PD的相关性的相关性 Cell, 2016, 167: 1469-1480; Pharmacology it is of better curative effect without damage to brain tissues.) 帕金森病的脑深部电刺激治疗帕金森病的脑深部电刺激治疗 1.3 .干细胞治疗干细胞治疗(Stem cell therapy) 近来帕金森病的治疗还发展了干细胞

21、移植及基因治疗等近来帕金森病的治疗还发展了干细胞移植及基因治疗等 手段。用于治疗帕金森病的干细胞主要有手段。用于治疗帕金森病的干细胞主要有胚胎干细胞胚胎干细胞、神神 经干细胞经干细胞、间充质干细胞间充质干细胞等。干细胞移植以及联合基因治等。干细胞移植以及联合基因治 疗在帕金森病的治疗上取得了一定的成果。疗在帕金森病的治疗上取得了一定的成果。 (In recent years, other treatments in PD have been developed, such as stem cell implantation and gene therapy. Stem cells used f

22、or PD treatment mainly include embryonic stem cell, neural stem cell and mesenchymal stem cells. Both stem cell transplant and combined gene therapy accomplished certain achievements in the treatment of PD.) 干细胞对帕金森病的治疗干细胞对帕金森病的治疗 Cell Stem Cell, 2014, 15: 653-665 图图10 临床前研究：临床前研究：从从hESCs衍生的神经元移植，可使

23、衍生的神经元移植，可使PD大鼠恢复运动功能。大鼠恢复运动功能。 1.4 基因治疗基因治疗(Gene therapy) 基因治疗主要通过三条途径：基因治疗主要通过三条途径： Gene therapy has three main pathways: 一、一、转染多巴胺合成途径中相关基因；转染多巴胺合成途径中相关基因； (Transfection of related genes in dopamine synthesis pathway.) 二、二、转染能合成神经营养因子的基因；转染能合成神经营养因子的基因； (Transfection of the genes involving in syn

24、thesization of neurotrophic factors.) 三、三、转染相关基因表达的调节基因。转染相关基因表达的调节基因。 (Transfection of the genes regulating gene expression.) 研究发现研究发现多基因的联合转染可提高对帕金森病的疗效多基因的联合转染可提高对帕金森病的疗效；同；同 时小干扰时小干扰RNA也逐渐应用于该病的研究圈。最近研究发现也逐渐应用于该病的研究圈。最近研究发现 通过小干扰通过小干扰RNAs可敲除特定的细胞可敲除特定的细胞mRNAs，从而抑制蛋，从而抑制蛋 白的表达，所以理论上白的表达，所以理论上RNAi

25、可以用于可以用于PD的治疗。已有实的治疗。已有实 验对验对a-synuclein、parkin的底物进行干扰以阻抑不同的凋的底物进行干扰以阻抑不同的凋 亡催化剂。亡催化剂。 (Study showed that combined transfection of multiple genes can enhance the curative effect of PD. And small interfering RNA (siRNA) has been applied to PD research to knock-out specific cellular messenger RNA (mRN

26、A), to inhibit protein expression. Theoretically, RNA interference (RNAi) can be used in the treatment of PD. Some experiments have been performed to interfere the substrates of -synuclein and parkin to inhibit different apoptosis catalysts.) 1.5 PD 临床治疗瓶颈（盲区与难点）及应对策略临床治疗瓶颈（盲区与难点）及应对策略(PD unmet clin

27、ical appeals and countermeasures ) 临床治疗瓶颈（难点、盲区）临床治疗瓶颈（难点、盲区） * “开关效应开关效应”：长期使用多巴胺能类药物产生药效波动 * 非运动症状：非运动症状：精神障碍、自主神经衰弱、睡眠障碍、多巴胺失调 综合征（嗜赌、嗜吃、疯狂购物等） 对应的研发策略对应的研发策略 *药物剂型改进药物剂型改进 *新药物新技术新方法研发新药物新技术新方法研发 * 中医药治疗中医药治疗 二）中医二）中医PD研究研究 1、文献溯源、文献溯源: 1)世界最早的病症记载：世界最早的病症记载：素问素问脉要精微论脉要精微论最早描述了震颤麻痹临床基最早描述了震颤麻痹临床

28、基 本特征。本特征。 (The description in Plain Questions Discussion on Truth share complete similarity with the main symptoms of PD, and it could be deemed as the earliest description of paralysis agitans). 2)世界最早的个案报道：世界最早的个案报道：金张子和关于金张子和关于“新寨马叟新寨马叟”的记载，是世界上第的记载，是世界上第 一例震颤麻痹的个案报道一例震颤麻痹的个案报道。 (Zhang Zihes rec

29、ord of old man Ma of Xin Zhai, in Jin Dynasty is the first case report of paralysis agitans in the world) 同时张子和用汗吐下三法治疗本病，开综合治疗之先河。同时张子和用汗吐下三法治疗本病，开综合治疗之先河。 (Zhang Zihe used perspiration, emetics and cathartics to treat paralysis agitans, which pioneered the comprehensive treatment of disease). 3）世界

30、最早的辨治体系：）世界最早的辨治体系： 明清以后PD中医病因病机认识趋于完善，并逐渐建立了辨证 论治体系。 (1) 致病因素：年迈体衰；风、虚、痰、火、瘀交互为病。致病因素：年迈体衰；风、虚、痰、火、瘀交互为病。 (2) 基本病机：属本虚标实之证，其中基本病机：属本虚标实之证，其中肝肾亏损、气血不足为致病之本，风肝肾亏损、气血不足为致病之本，风 、火、痰、瘀为致病之标、火、痰、瘀为致病之标。 (3) 辨证要点辨证要点 实证：一般震颤较剧，肢体僵硬，烦燥不宁，胸闷体胖，遇郁怒而发者；实证：一般震颤较剧，肢体僵硬，烦燥不宁，胸闷体胖，遇郁怒而发者； 虚证：颤抖无力，缠绵难愈，腰膝酸软，体瘦眩晕，遇

31、烦劳而加重者；虚证：颤抖无力，缠绵难愈，腰膝酸软，体瘦眩晕，遇烦劳而加重者；病病 久常标本虚实夹杂久常标本虚实夹杂 2、现代中医诊疗、现代中医诊疗 2.1.分型论治是中医诊疗的主流分型论治是中医诊疗的主流 (Treatment based on syndrome differentiation is the mainstream of TCM in the treatment of PD) 2.1.1.王永炎分三型王永炎分三型（中医杂志，（中医杂志，1986, (8):22 ） Wang Yongyan classified PD into 3 types (Journal of Tradit

32、ional Chinese Medicine, 1986, (8):22) 气血两虚，血虚动风型气血两虚，血虚动风型黄芪、党参、当归、白芍、天麻黄芪、党参、当归、白芍、天麻 、钩藤、珍珠母、丹参、鸡血藤、羚羊角粉。、钩藤、珍珠母、丹参、鸡血藤、羚羊角粉。 (Deficiency of qi and blood, wind stirring due to blood stasis: Huang Qi (Radix Astragali), Dang Shen (Radix Codonopsis), Dang Gui (Radix Angelicae Sinensis), Bai Shao (Rad

33、ix Paeoniae Alba), Tian Ma (Rhizoma Gastrodiae), Gou Teng (Ramulus Uncariae cum Uncis), Zhen Zhu Mu (Concha Margaritifera Usta), Dan Shen (Radix Salviae Miltiorrhizae), Ji Xue Teng (Caulis Spatholobi), Ling Yang Jiao (Cornu Saigae Tataricae) powder.) 肝肾不足，血瘀动风型肝肾不足，血瘀动风型生熟地、何首乌、玄参、钩藤、生熟地、何首乌、玄参、钩藤、

34、羚羊角粉、生牡蛎、丹参、赤芍等。羚羊角粉、生牡蛎、丹参、赤芍等。 (Deficiency of liver and kidney, wind stirring due to blood stasis: Sheng Di Huang (Radix Remanniae), Shu Di Huang (Radix Remanniae Prepparata), He Shou Wu (Radix Polygoni Multiflori), Xuan Shen (Radix Scrophulariae), Gou Teng (Ramulus Uncariae cum Uncis), Ling Yang

35、Jiao (Cornu Saigae Tataricae) powder, Sheng Mu Li (Concha Ostreae), Dan Shen (Radix Salviae Miltiorrhizae), Chi Shao (Radix Paeoniae Rubra), and so on.) 痰热动风型痰热动风型全瓜篓、胆南星、竹沥、钩藤、天麻、羚羊全瓜篓、胆南星、竹沥、钩藤、天麻、羚羊 角粉、珍珠母、丹参、赤芍等。角粉、珍珠母、丹参、赤芍等。 (Wind stirring due to phlegm heat: Quan Gua Lou (Fructus Trichosanthi

36、s), Dan Nan Xing (), Zhu Li (Succus Phyllostachydis Henonis), Gou Teng (Ramulus Uncariae cum Uncis), Tian Ma (Rhizoma Gastrodiae), Ling Yang Jiao (Cornu Saigae Tataricae) powder, Zhen Zhu Mu (Concha Margaritifera Usta), Dan Shen (Radix Salviae Miltiorrhizae), Chi Shao (Radix Paeoniae Rubra), and so

37、on.) 2.1.2.任继学（江苏中医杂志，任继学（江苏中医杂志，1982, (4):11 ），提出五个证型：），提出五个证型： Ren Jixue classified PD into five types (Jiangsu Journal of Traditional Chinese Medicine, 1982; (4):11) 风阳内动风阳内动滋生清阳汤滋生清阳汤 Wind Yang and internal agitation: Zisheng Qingyang Tang 髓海不足髓海不足延寿翁头汤延寿翁头汤 Deficiency of the sea of marrow: Yang

38、shou Wengtou Tang 阳虚气弱阳虚气弱补中益气汤补中益气汤 Deficiency of yang and weakness of qi: Buzhong Yiqi Tang 心虚血少心虚血少天王补心丹或炙甘草汤天王补心丹或炙甘草汤 Weakness of heart and deficiency of blood: Tianwang Buxin Dan or Zhigancao Tang 痰涎雍滞痰涎雍滞二陈汤加煨皂角、硼砂等二陈汤加煨皂角、硼砂等 Stasis of phlegm and saliva: Erchen Tang plus roasted Zao Jiao (Sp

39、ina Gleditsiae), Peng Sha (Borax), and so on. 2.2.专方专药：经方、古方或自拟方。专方专药：经方、古方或自拟方。 Special formula and special drug: classical formula, ancient formula and self-drafted formula 张沛虬、李怀生用王肯堂的定震丸；张沛虬、李怀生用王肯堂的定震丸； Dingzhen Wan, invented by Wang Kentang, used by Zhang Peiqiu and Li Huaisheng. 李香玉用杞菊地黄丸；李香玉

40、用杞菊地黄丸； (Qiju Dihuang Wan used by Li Xiangyu.) 马力行用六味地黄丸；马力行用六味地黄丸； (Liuwei Dihuang Wan used by Ma Lixing.) 陆益民用逍遥丸等。陆益民用逍遥丸等。 (Xiaoyao Wan used by Lu Yimin et al. ) 北京中医药大学东直门医院的平颤片北京中医药大学东直门医院的平颤片 Ping Chan Pian used in Dongzhimen Hospital of Beijing University of Chinese Medicine 上海市中西医结合医院的平颤一号汤

41、上海市中西医结合医院的平颤一号汤 Pingchan Yihao Tang used in ShanghaiTCM-Integrated Hospital 河南省中医院的龟羚帕安丸河南省中医院的龟羚帕安丸 Guiling Paan Wan used in Henan TCM Hospital 我们的科研制剂安颤灵我们的科研制剂安颤灵 An Chan Ling developed by our institute. 镇肝熄风汤：镇肝熄风汤：meta分析表明，镇肝熄风汤或镇肝熄风汤联合美多巴、美分析表明，镇肝熄风汤或镇肝熄风汤联合美多巴、美 多巴多巴+常规西药效果均优于美多巴、美多巴常规西药效果均优

42、于美多巴、美多巴+常规西药。常规西药。 都属于帕金森病的专方专药治疗都属于帕金森病的专方专药治疗。 All of them belong to the special formula and special drug in the treatment of PD. 个人认为，专方专药这是研究治疗的重要方向。个人认为，专方专药这是研究治疗的重要方向。 From my perspective, special formula and special drug are the future of the treatment of PD. 2.3.2.3.单味中药单味中药 (Single Chines

43、e herb) 目前采用现代医学的实验方法尚未发现某种中药中含有治疗的有效成分目前采用现代医学的实验方法尚未发现某种中药中含有治疗的有效成分 或单体，但临床研究确实发现了一些可喜的苗头。或单体，但临床研究确实发现了一些可喜的苗头。 (So far, using experimental method of modern medicine, no effective component or monomer was found in the Chinese herb to treat PD. But some promising results came out in clinical rese

44、arch.) 大量临床研究发现羚羊角粉是通治震颤不可缺少的主药；大量临床研究发现羚羊角粉是通治震颤不可缺少的主药； (Certain studies suggest that Ling Yang Jiao (Cornu Saigae Tataricae) powder is an indispensable basic remedy in the treatment of tremor. ) 上海第二医学院附属三院用中药洋金花制剂麻醉时，意外发现麻醉后的上海第二医学院附属三院用中药洋金花制剂麻醉时，意外发现麻醉后的 病人，在病人，在2-24日内震颤症状消失。日内震颤症状消失。 (When Ya

45、ng Jin Hua (Flos Daturae) was used as anaesthetic in the No.3 Hospital of Shanghai the Second Medical College, tremor symptoms disappeared in PD patients 2-24 days after anaesthesia.) 3 3、中西医结合治疗、中西医结合治疗 Therapy by integrative Chinese and western medicine 对于对于PDPD的药物治疗，目前除左旋多巴外，还不断研制推出了许多新的药的药物治疗，目前

46、除左旋多巴外，还不断研制推出了许多新的药 物。各种治疗药物虽能使物。各种治疗药物虽能使PDPD患者的临床症状在一定的时间内获得一定患者的临床症状在一定的时间内获得一定 程度的好转但均不能阻止本病的自然进程，且各种药物都有不同程程度的好转但均不能阻止本病的自然进程，且各种药物都有不同程 度的副反应，因而限制了其自身在临床上的应用。近年来中西药联合度的副反应，因而限制了其自身在临床上的应用。近年来中西药联合 应用治疗本病，不仅提高了临床疗效，而且大大降低了西药的用量和应用治疗本病，不仅提高了临床疗效，而且大大降低了西药的用量和 副作用。副作用。 Besides levodopa, many nov

47、el medications for PD are being developed currently. Each drug can relieve the symptoms to some degree, but none of them can stop its natural progression. And each drug has its own side- effects. Therefore, their application in clinical practice is limited. Recently, integrative Chinese and western

48、medicine has been adopted to treat this disease which not only enhance the clinical effects but also severely reduce the dosage and side effects of western medicine. 3.1 中药与美多巴联用中药与美多巴联用 TCM combined with madopar 马龙将临床观察病例随机分为对照组和治疗组。两组均马龙将临床观察病例随机分为对照组和治疗组。两组均 服用美多巴标准片，根据病情需要或毒副反应适当加减调整服用美多巴标准片，根据病

49、情需要或毒副反应适当加减调整 剂量。治疗组同时给予中药熄风定颤丸剂量。治疗组同时给予中药熄风定颤丸( (龟板、制首乌、天龟板、制首乌、天 麻、白僵蚕、白芍、川芎、石菖蒲等麻、白僵蚕、白芍、川芎、石菖蒲等) )。对照组给予安慰剂。对照组给予安慰剂 ，疗程，疗程1212周。周。 (Ma Long divided the cases into control and treatment groups randomly. Patients in both groups were given standard madopar tablet and the dosage was adjusted acco

50、rding to the severity of illness and adverse reaction. Patients in treatment group were also given TCM Xifeng Dinchan Wan (Gui Ban (Carapax et Plastrum Testudinis), Zhi Shou Wu (Radix Polygoni Multiflori Praeparata), Tian Ma (Rhizoma Gastrodiae), Bai Jiang Can (Bombyx Batryticatus), Bai Shao (Radix

51、Paeoniae Alba), Chuan Xiong (Rhizoma Chuanxiong), Shi Chang Pu (Rhizoma Acori Tatarinowii), and so on), while patients in control group given placebo, and the therapy lasted for 12 weeks. ) 结果治疗组总有效率为结果治疗组总有效率为90.O90.O明显高于对照组的明显高于对照组的62.562.5 ：治疗组的中医症状、生存质量改善情况明显优于对照组；：治疗组的中医症状、生存质量改善情况明显优于对照组； 而治疗组

52、药物毒副症状积分较对照组下降更为显著。证明熄而治疗组药物毒副症状积分较对照组下降更为显著。证明熄 风定颤丸合用美多巴治疗因服西药疗效衰减并出现明显毒副风定颤丸合用美多巴治疗因服西药疗效衰减并出现明显毒副 反应的帕金森病患者，能明显提高患者生存质量，减轻毒副反应的帕金森病患者，能明显提高患者生存质量，减轻毒副 反应，增强原有疗效。同时临床运用比较安全。反应，增强原有疗效。同时临床运用比较安全。 (The effective rate in treatment group was 90.0%, much higher than that in control group (62.5%); impr

53、ovement of TCM symptoms and life quality was better than that in control group; the decrease of toxic and adverse reaction was more evident in treatment group than that in control group. It suggested combined use of Xifeng Dinchuan Wan and madopar in the PD patients who showed obvious toxic and adve

54、rse reaction due to the wearing off of western medicine, could significantly improve the life quality of PD patients, alleviate the toxic effects and enhance the therapeutic effects. The combined application in clinic is safe. ) 3.2 中药与盐酸舍曲林联用中药与盐酸舍曲林联用 TCM combined with sertraline hydrochloride 马云枝

55、等马云枝等 帕金森病伴抑郁状态患者随机分为治疗组，帕金森病伴抑郁状态患者随机分为治疗组， 给予柴胡疏肝散给予柴胡疏肝散( (柴胡、白芍、枳壳、陈皮、木香、香附、柴胡、白芍、枳壳、陈皮、木香、香附、 川芎、炙甘草等川芎、炙甘草等) )联合盐酸舍曲林片治疗，对照组口服盐酸联合盐酸舍曲林片治疗，对照组口服盐酸 舍曲林片治疗。舍曲林片治疗。 (Ma Yunzhi et al. divided the PD patient with depression into two groups randomly. TCM group was given Chaihu Shugan San (Chai Hu (R

56、adix Bupleuri),Bai Shao (Radix Paeoniae Alba), Zhi Qiao (Fructus Aurantii), Chen Pi (Pericarpium Citri Reticulatae), Mu Xiang (Radix Aucklandiae), Xiang Fu (Rhizoma Cyperi), Zhi Gan Cao (Radix Glycyrrhizae Praeparatae), and so on) combined with sertraline hydrochloride; the control group was given s

57、ertraline hydrochloride orally. ) 结果治疗结果治疗8 8周后两组汉密尔顿抑郁量表周后两组汉密尔顿抑郁量表(HAMD)(HAMD)评分与评分与 治疗前相比均有显著差异治疗前相比均有显著差异(P0.05)(P0.05)；两组间比较，差异有；两组间比较，差异有 统计学意义统计学意义(P0.05)(P0.05)；治疗后两组患者中医证候积分较治；治疗后两组患者中医证候积分较治 疗前下降，观察组治疗后中医证候积分较对照组明显下降疗前下降，观察组治疗后中医证候积分较对照组明显下降 (P0.05)(P0.05)。证明柴胡疏肝散加减联合盐酸舍曲林片治疗帕。证明柴胡疏肝散加减联合

58、盐酸舍曲林片治疗帕 金森伴抑郁状态疗效更优于单用舍曲林组。金森伴抑郁状态疗效更优于单用舍曲林组。 (Eight weeks after therapy, Hamilton depressive scale (HAMD) score in both groups showed remarkable difference compared with before the treatment (P 0.05); comparison between two groups also showed significant difference (P 0.05); TCM syndrome score i

59、n both groups decreased after therapy, and the decrease in TCM group was more evident than that in control group (P 0.05). It confirmed combined administration of Chaihu Shugan San had better therapeutic effects than the single administration of sertraline hydrochloride.) 四、发展展望四、发展展望(Prospect) 1. 现

60、代医学现有对现代医学现有对PD 的药物治疗主要是改善和控制症状，但因的药物治疗主要是改善和控制症状，但因 西药本身固有的缺陷如长期应用疗效减退、耐药及其本身存西药本身固有的缺陷如长期应用疗效减退、耐药及其本身存 在的毒副作用等，导致其在临床上的应用有一定的局限性；在的毒副作用等，导致其在临床上的应用有一定的局限性； 2. 中医药具有独特疗效，如可随证加减、可针对个体调整用药、中医药具有独特疗效，如可随证加减、可针对个体调整用药、 毒副作用较小等；中西医结合用药，能明显改善患者的运动毒副作用较小等；中西医结合用药，能明显改善患者的运动 症状和认知功能，降低抗症状和认知功能，降低抗PD西药的用量，