帕金森病的中西醫(yī)結(jié)合研究現(xiàn)狀與展望課件

1、帕金森病中西醫(yī)結(jié)合診療研究現(xiàn)狀與展望Clinical Overview and Research Prospects of Parkinsons disease in the Integrative Chinese and Western Medicine一、帕金森病概述Definition of Parkinsons disease (PD)帕金森?。≒D）:又稱震顫麻痹。是一種原因不明的、慢性進(jìn)行性加重的中樞神經(jīng)系統(tǒng)變性性疾病。 ( Parkinsons disease (PD), also called paralysis agitans, is a chronic, progressi

2、ve degenerative disorder of the central nervous system of unknown causes). 臨床上以錐體外系運(yùn)動障礙為特征，表現(xiàn)為運(yùn)動徐緩、靜止性震顫和強(qiáng)直,此外病人還可出現(xiàn)吞咽困難，自主神經(jīng)功能障礙和癡呆。 (Clinically it is characterized by the motor symptoms of extrapyramidal system, manifesting as slowness of movement, static tremor and rigidity. Patient with PD also

3、displays dysphagia, autonomic dysfunction and dementia). 圖1 PD患病率與年齡、地區(qū)的相關(guān)性研究Movement disorders, 2014, 29: 1583-1590PD 在65 歲以上西方人群中的患病率約0.1% 0.25%；在中國患病率約1.7%。臨床特征：以錐體外系運(yùn)動障礙為主，表現(xiàn)為運(yùn)動徐緩、靜止性震顫和強(qiáng)直；還可出現(xiàn)吞咽困難，自主神經(jīng)功能障礙和癡呆。 (Clinically it is characterized by the motor symptoms of extrapyramidal system, manif

4、esting as slowness of movement, static tremor and rigidity. Patient with PD also displays dysphagia, autonomic dysfunction and dementia). 圖2 PD運(yùn)動癥狀（左）和非運(yùn)動癥狀（右）Nature review, 2017, 18: 435-450其特征性病理改變是中腦黑質(zhì)多巴胺神經(jīng)元的缺失，以及黑質(zhì)神經(jīng)元內(nèi)出現(xiàn)Lewy小體。 (Its characteristic pathological changes include the death of dopami

5、nergic neurons in the substantia nigra, a region of the midbrain and the appearance of Lewy body in residual neurons of substantia nigra).圖3 PD的病理特征Nature review, 2017, 18: 251-259圖4 PD200年研究的編年史-I縮寫：ALS：肌萎縮性脊髓側(cè)索硬化癥；Nature review, 2017, 18: 251-259圖5 PD200年研究的編年史-IIGBA：葡溏苷酰鞘氨醇酶；LAG3：淋巴細(xì)胞激活基因3；L-DOPA

6、：左旋多巴；MPTP：1-甲級-4-苯基-1,2,5,6-四羥基吡啶；SNCA：-突觸核蛋白二、基礎(chǔ)醫(yī)學(xué)研究進(jìn)展Research overview of modern medicine（一）病因與發(fā)病因素：帕金森病(PD)為第二大神經(jīng)退行性疾病，大多數(shù)PD 患者呈散發(fā)性，其中約10% 15% 的患者有家族史；其發(fā)病可能與遺傳、環(huán)境、年齡老化、免疫炎癥、細(xì)胞凋亡、線粒體功能障礙等諸多因素有關(guān)。一般認(rèn)為，本病的發(fā)生是遺傳與環(huán)境因素相互作用的結(jié)果。 （Pathogenesis and pathogenic factors： PD is one of most common age-related n

7、eurodegenerative 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, immune inflammation, apotosis, mitochondrial dysfunction and so on. It is generally acknowledged that it is the consequence of inter

8、action of gene and environmental factors）. （二）分子流行病學(xué)研究：研究發(fā)現(xiàn)與帕金森病發(fā)病有關(guān)的基因已達(dá)21個。Fig.1 Simplified workflows for whole-exome, whole-genome 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 gen

9、es identified by GWASRef: Molecular and Cellular Probes, 2016, 30: 386-396.Gene (locus)MethodologyClinical phenotypeVPS35Exome sequencingTypical, late-onset PDSYT11, ACMSD, STK39, MCCC1/LAMP3; GAK, BST1, SNCA, HLA-DRB5, LRRK2, CCDC62/HIP1R, MAPTGWASFamilial or sporadic PDPARK16, STBD1, GPNMB, FGF20,

10、 STX1BGWASUnknownSCARB2, SREBF1/RAI1GWASEarly-onset and late-onset PDTNK2, TNRWESFamilial PDGWAS: genome-wide association studies Table 1 Confirmed genes implicated in monogenic PDRef: Nature Reviews Neuroscience, 2012, 13:453-464. Ann. Transl. Med., 2014;2(12):125.JAMA Neurology, 2016;73(1):68-75Ge

11、ne (locus)MethodologyClinical phenotypeCEL, MPHOSPH10, TAS2R19, SERPINA1WES/GWASEarly-onsetPDGPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13CWESSporadic PDDNAJC6WESJuvenile onset, atypical PDSYNJ1Exome sequencingJuvenile onset, atypical PDEIF4G1WESGPATCH2L, UHRF1BP1L, PTPRH, ARSB, VPS13CWESFamilial PDWE

12、S: Whole-exome sequencingTable 1 Confirmed genes implicated in monogenic PD (continued)Ref: Neurobiology of Aging, 2017, 195: e7-e10. Genome Biology, 2017, 18: 22.Parkinsonism and Related Disorders, 2014, S23S28其中最重要的為PARK1基因突變： (Molecular epidemiology research：Nine genes related to PD have been fou

13、nd. Some popular genes see as follows): a-突觸核蛋白(a-synuclein)定位于4q21-23，為PARK1基因突變，是腦內(nèi)一種突觸前蛋白，與家族性早發(fā)帕金森病密切相關(guān)，是散發(fā)性帕金森病和其他神經(jīng)退行性病變中路易小體的主要成分。 (a-synuclein positioned on 4q21-23 is the genetic mutation of PARK1. It is a presynaptic protein existing in brain, closely related to familial early-onset PD, wi

14、tch is the major component of Lewy body in sporadic PD and other neurodegenerative diseases). （三）分子病理學(xué)研究：構(gòu)象病是當(dāng)代醫(yī)學(xué)發(fā)展具有里程碑意義的分子醫(yī)學(xué)新概念，為諸多重大疑難疾病由傳統(tǒng)的姑息性治療向根治性治療轉(zhuǎn)變帶來了突破的新希望。構(gòu)象病即是由分子構(gòu)象異常的錯誤折疊蛋白質(zhì)積聚導(dǎo)致的一類疾病，錯誤折疊蛋白質(zhì)積聚導(dǎo)致ERS相關(guān)細(xì)胞凋亡是蛋白質(zhì)構(gòu)象病的核心分子病理機(jī)制。 (New concept in Molecular pathology: Conformational disease, a ne

15、w concept in molecular medicine, is a landmark in the development of modern medicine. It brings breakthrough and new hope to many gravely difficult diseases from traditional palliative treatment to radical treatment. Conformational disease is a kind of disease resulted from accumulation of misfolded

16、 abnormal molecular conformation proteins. Accumulation of misfolded proteins results in the apoptosis of ERS, which is the core of molecular pathological mechanism. Recently, many researches show that PD is a typical neurodegenerative conformational disease, and dysfunction accumulation and degrada

17、tion of misfolded -synuclein is the key step in PDs pathogenesis)圖6 PD信號轉(zhuǎn)導(dǎo)相互作用通路圖Cell Signaling Technology, 2012 Neuron, 2016, 90: 675-691 圖7 PD中-突觸核蛋白聚集及纖維化（四）腸道菌群與PD：近期Cell一項(xiàng)顛覆性研究成果發(fā)現(xiàn)腸道菌群失調(diào)是PD的罪魁禍?zhǔn)?，為PD的防治開辟了全新的方向。研究識別到十幾個屬的腸道微生物可能介導(dǎo)PD發(fā)生；腸道微生物失調(diào)可能導(dǎo)致-syn錯誤折疊、通過腦腸軸影響包括中樞神經(jīng)、自主神經(jīng)及腸道周圍神經(jīng)在內(nèi)的各級神經(jīng)功能，并與PD患者

18、非運(yùn)動癥狀和運(yùn)動癥狀密切相關(guān).圖8 腦-腸-微生物對話與PD的相關(guān)性Cell, 2016, 167: 1469-1480; Pharmacology & Therapeutics, 2016, 158: 52-62. 圖9 腦腸軸與PD非運(yùn)動癥狀的相關(guān)性Parkinsonism and Related Disorders, 2016, 27: 1-8. （五）帕金森病發(fā)病新學(xué)說 帕金森病的生物學(xué)變化在早期發(fā)育就開始 Le et al, Neuroscientists, 200822三、帕金森病的臨床診斷與治療進(jìn)展 實(shí)現(xiàn)早期診斷的關(guān)鍵在于 “前驅(qū)期”帕金森病的病理改變和癥狀發(fā)展不平行Braak（

19、病理）分期臨床癥狀嗅覺減退便秘睡眠障礙抑郁立體視覺障礙I單側(cè)震顫肌強(qiáng)直運(yùn)動不能II雙側(cè)肢體疾病III平衡障礙IV跌倒部分依賴性認(rèn)知功能下降V活動受限完全依賴癡呆520年前驅(qū)癥狀1015年運(yùn)動癥狀0+10y+20y-10y-20y1233456病理改變H & Y（臨床）分期臨床診斷一）早期診斷非運(yùn)動癥狀 頻率（%） 特異性（%） 風(fēng)險(xiǎn)增加系數(shù)（倍數(shù)）嗅覺減退 85 60 1.5 RBD 65 75 2.5 抑郁 60 70 0.8 便秘 55 45 0.6 站立性低血壓 25 65 0.5 立體視覺障礙 30 60 0.3 明確的家族史 10 90 2.5神經(jīng)毒物接觸史 8 55 1.0總結(jié) 9

20、.7倍 帕金森病的早期診斷：運(yùn)動前驅(qū)癥像研究、 項(xiàng)目背景和研究內(nèi)容-更改Giasson and Lee, 2013PD-synucleinopathies -突觸蛋白病25（三）主要研究內(nèi)容與關(guān)鍵技術(shù)基于風(fēng)險(xiǎn)預(yù)測和生物標(biāo)記，研發(fā)個體化的PD 早期診斷決策系統(tǒng)建設(shè)完整規(guī)范的前驅(qū)期PD 的臨床、實(shí)驗(yàn)室和影像數(shù)據(jù)庫包括臨床、實(shí)驗(yàn)室和影像數(shù)據(jù)4年隨訪動態(tài)數(shù)據(jù)發(fā)現(xiàn)PD 早期診斷標(biāo)志物，研發(fā)相關(guān)檢測技術(shù)和產(chǎn)品體液和組織標(biāo)記無創(chuàng)的影像學(xué)客觀標(biāo)記研發(fā)新技術(shù)確定中國人罹患PD 的遺傳學(xué)及環(huán)境風(fēng)險(xiǎn)因素，建立PD 發(fā)病的風(fēng)險(xiǎn)預(yù)測模型驗(yàn)證致病和易感基因，篩選遺傳標(biāo)志物分析環(huán)境與遺傳交互作用把帕金森病的臨床診斷從臨床期

21、提前到前驅(qū)期帕金森病的早期診斷研究、26 帕金森病早期診斷研究主要從體液和組織中尋找帕金森病的特異性生物標(biāo)記-synuclein影像技術(shù)僅限于超聲和PET/SPECTDJ-1Apo1ParkinUbiquitin 測量結(jié)果一致性不高 腦脊液和組織不易獲得國內(nèi)尚需開發(fā)高靈敏的診斷PD的影像產(chǎn)品主觀性大不能定量臨床期患者 帕金森病的生物學(xué)標(biāo)記研究二）臨床治療(Treatment)治療(Treatment)現(xiàn)代醫(yī)學(xué)治療Western medicine中醫(yī)治療Treatment in TCM中西醫(yī)結(jié)合治療 Therapy by integrative Chinese and western medic

22、ine藥物治療Drug therapy 外科治療Surgical therapy干細(xì)胞治療Stem cell therapy基因治療Gene therapy分證論治 Treatment based on syndrome differentiation 專方專藥 Special formula and special drug單味中藥 Single Chinese herb針灸與針?biāo)幒嫌肁cupuncture and moxibustion combined with medicin1、現(xiàn)代醫(yī)學(xué)治療 1.1.藥物治療： 研究證實(shí)，PD 早期神經(jīng)保護(hù)治療可以延緩病情發(fā)展，延后左旋多巴的應(yīng)用，對整

23、個病程是有益的。對于早期輕癥患者，推薦單胺氧化酶( MAO-B) 抑制劑和多巴胺受體激動劑治療，以延緩左旋多巴的應(yīng)用。 (Drug therapy: It is confirmed that early protection of nervous system could delay the progression of PD, and application of levodopa, which is beneficial to the disease development. For the patients with mild symptoms at early stage, monoa

24、mine oxidase (MAO)-B inhibitor and dopamine receptor agonists are recommended to delay the application of levodopa.)圖10 PD多巴胺能藥物及其作用機(jī)理1.2 外科治療(Surgical therapy) 外科手術(shù)治療帕金森病以腦立體定向毀損術(shù)為代表，創(chuàng)傷較大且適用范圍較窄，臨床預(yù)后效果尚待改善。另外一種外科手段為深部電刺激，應(yīng)用立體定向技術(shù)將電極植入腦內(nèi)的不同部位，通過高頻電流刺激靶點(diǎn)達(dá)到治療目的，但不破壞腦組織且療效較好。 (Stereotactic ablative bra

25、in surgery is the major surgical therapy of PD, such as pallidotomy or pallidotomy + VIM-thalamotomy. Ablation has large damage and narrow scope of application, the clinical prognosis still needs to be improved. Another surgery operation is called deep brain stimulation (DBS), which implants electro

26、des in different brain area with stereotactic technique and stimulates target point through high-frequency current; it is of better curative effect without damage to brain tissues.)帕金森病的腦深部電刺激治療1.3 .干細(xì)胞治療(Stem cell therapy) 近來帕金森病的治療還發(fā)展了干細(xì)胞移植及基因治療等手段。用于治療帕金森病的干細(xì)胞主要有胚胎干細(xì)胞、神經(jīng)干細(xì)胞、間充質(zhì)干細(xì)胞等。干細(xì)胞移植以及聯(lián)合基因治療在

27、帕金森病的治療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 for PD treatment mainly include embryonic stem cell, neural stem cell and mesenchymal stem cells. Both stem cell transplant and combined gene therapy accom

28、plished certain achievements in the treatment of PD.)干細(xì)胞對帕金森病的治療Cell Stem Cell, 2014, 15: 653-665圖10 臨床前研究：從hESCs衍生的神經(jīng)元移植，可使PD大鼠恢復(fù)運(yùn)動功能。1.4 基因治療(Gene therapy) 基因治療主要通過三條途徑： Gene therapy has three main pathways:一、轉(zhuǎn)染多巴胺合成途徑中相關(guān)基因； (Transfection of related genes in dopamine synthesis pathway.)二、轉(zhuǎn)染能合成神經(jīng)營養(yǎng)

29、因子的基因； (Transfection of the genes involving in synthesization of neurotrophic factors.)三、轉(zhuǎn)染相關(guān)基因表達(dá)的調(diào)節(jié)基因。 (Transfection of the genes regulating gene expression.) 研究發(fā)現(xiàn)多基因的聯(lián)合轉(zhuǎn)染可提高對帕金森病的療效；同時(shí)小干擾RNA也逐漸應(yīng)用于該病的研究圈。最近研究發(fā)現(xiàn)通過小干擾RNAs可敲除特定的細(xì)胞mRNAs，從而抑制蛋白的表達(dá)，所以理論上RNAi可以用于PD的治療。已有實(shí)驗(yàn)對a-synuclein、parkin的底物進(jìn)行干擾以阻抑不同的凋

30、亡催化劑。 (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 (mRNA), to inhibit protein expression. Theoretically, RNA interference (RNAi) can be

31、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 臨床治療瓶頸（盲區(qū)與難點(diǎn)）及應(yīng)對策略(PD unmet clinical appeals and countermeasures )臨床治療瓶頸（難點(diǎn)、盲區(qū)）“開關(guān)效應(yīng)”：長期使用多巴胺能類藥物產(chǎn)生藥效波動 非運(yùn)動癥狀：精神障礙、自主神經(jīng)衰弱、睡眠障礙、多巴胺失調(diào)

32、綜合征（嗜賭、嗜吃、瘋狂購物等）對應(yīng)的研發(fā)策略藥物劑型改進(jìn)新藥物新技術(shù)新方法研發(fā) 中醫(yī)藥治療二）中醫(yī)PD研究1、文獻(xiàn)溯源: 1)世界最早的病癥記載：素問脈要精微論最早描述了震顫麻痹臨床基本特征。 (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)世界最早的個案報(bào)道：金張子和

33、關(guān)于“新寨馬叟”的記載，是世界上第一例震顫麻痹的個案報(bào)道。 (Zhang Zihes record of old man Ma of Xin Zhai, in Jin Dynasty is the first case report of paralysis agitans in the world) 同時(shí)張子和用汗吐下三法治療本病，開綜合治療之先河。 (Zhang Zihe used perspiration, emetics and cathartics to treat paralysis agitans, which pioneered the comprehensive treatm

34、ent of disease). 3）世界最早的辨治體系： 明清以后PD中醫(yī)病因病機(jī)認(rèn)識趨于完善，并逐漸建立了辨證論治體系。(1) 致病因素：年邁體衰；風(fēng)、虛、痰、火、瘀交互為病。(2) 基本病機(jī)：屬本虛標(biāo)實(shí)之證，其中肝腎虧損、氣血不足為致病之本，風(fēng)、火、痰、瘀為致病之標(biāo)。(3) 辨證要點(diǎn)實(shí)證：一般震顫較劇，肢體僵硬，煩燥不寧，胸悶體胖，遇郁怒而發(fā)者；虛證：顫抖無力，纏綿難愈，腰膝酸軟，體瘦眩暈，遇煩勞而加重者；病久常標(biāo)本虛實(shí)夾雜2、現(xiàn)代中醫(yī)診療2.1.分型論治是中醫(yī)診療的主流 (Treatment based on syndrome differentiation is the mainst

35、ream of TCM in the treatment of PD)2.1.1.王永炎分三型（中醫(yī)雜志，1986, (8):22 ） Wang Yongyan classified PD into 3 types (Journal of Traditional Chinese Medicine, 1986, (8):22)氣血兩虛，血虛動風(fēng)型黃芪、黨參、當(dāng)歸、白芍、天麻、鉤藤、珍珠母、丹參、雞血藤、羚羊角粉。 (Deficiency of qi and blood, wind stirring due to blood stasis: Huang Qi (Radix Astragali),

36、Dang Shen (Radix Codonopsis), Dang Gui (Radix Angelicae Sinensis), Bai Shao (Radix 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 (Co

37、rnu Saigae Tataricae) powder.)肝腎不足，血瘀動風(fēng)型生熟地、何首烏、玄參、鉤藤、羚羊角粉、生牡蠣、丹參、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 (R

38、amulus Uncariae cum Uncis), Ling Yang Jiao (Cornu Saigae Tataricae) powder, Sheng Mu Li (Concha Ostreae), Dan Shen (Radix Salviae Miltiorrhizae), Chi Shao (Radix Paeoniae Rubra), and so on.)痰熱動風(fēng)型全瓜簍、膽南星、竹瀝、鉤藤、天麻、羚羊角粉、珍珠母、丹參、赤芍等。 (Wind stirring due to phlegm heat: Quan Gua Lou (Fructus Trichosanthis)

39、, 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 on

40、.)2.1.2.任繼學(xué)（江蘇中醫(yī)雜志，1982, (4):11 ），提出五個證型： Ren Jixue classified PD into five types (Jiangsu Journal of Traditional Chinese Medicine, 1982; (4):11)風(fēng)陽內(nèi)動滋生清陽湯 Wind Yang and internal agitation: Zisheng Qingyang Tang 髓海不足延壽翁頭湯 Deficiency of the sea of marrow: Yangshou Wengtou Tang 陽虛氣弱補(bǔ)中益氣湯 Deficiency of

41、yang and weakness of qi: Buzhong Yiqi Tang心虛血少天王補(bǔ)心丹或炙甘草湯 Weakness of heart and deficiency of blood: Tianwang Buxin Dan or Zhigancao Tang痰涎雍滯二陳湯加煨皂角、硼砂等 Stasis of phlegm and saliva: Erchen Tang plus roasted Zao Jiao (Spina Gleditsiae), Peng Sha (Borax), and so on. 2.2.專方專藥：經(jīng)方、古方或自擬方。 Special formula

42、and special drug: classical formula, ancient formula and self-drafted formula 張沛虬、李懷生用王肯堂的定震丸； Dingzhen Wan, invented by Wang Kentang, used by Zhang Peiqiu and Li Huaisheng. 李香玉用杞菊地黃丸； (Qiju Dihuang Wan used by Li Xiangyu.) 馬力行用六味地黃丸； (Liuwei Dihuang Wan used by Ma Lixing.) 陸益民用逍遙丸等。 (Xiaoyao Wan us

43、ed by Lu Yimin et al. ) 北京中醫(yī)藥大學(xué)東直門醫(yī)院的平顫片 Ping Chan Pian used in Dongzhimen Hospital of Beijing University of Chinese Medicine 上海市中西醫(yī)結(jié)合醫(yī)院的平顫一號湯 Pingchan Yihao Tang used in ShanghaiTCM-Integrated Hospital 河南省中醫(yī)院的龜羚帕安丸 Guiling Paan Wan used in Henan TCM Hospital 我們的科研制劑安顫靈 An Chan Ling developed by our

44、 institute. 鎮(zhèn)肝熄風(fēng)湯：meta分析表明，鎮(zhèn)肝熄風(fēng)湯或鎮(zhèn)肝熄風(fēng)湯聯(lián)合美多巴、美多巴+常規(guī)西藥效果均優(yōu)于美多巴、美多巴+常規(guī)西藥。都屬于帕金森病的專方專藥治療。All of them belong to the special formula and special drug in the treatment of PD. 個人認(rèn)為，專方專藥這是研究治療的重要方向。From my perspective, special formula and special drug are the future of the treatment of PD. 2.3.單味中藥 (Single C

45、hinese herb)目前采用現(xiàn)代醫(yī)學(xué)的實(shí)驗(yàn)方法尚未發(fā)現(xiàn)某種中藥中含有治療的有效成分或單體，但臨床研究確實(shí)發(fā)現(xiàn)了一些可喜的苗頭。 (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 research.) 大量臨床研究發(fā)現(xiàn)羚羊角粉是通治震顫不可缺少的主藥； (Certain studies

46、suggest that Ling Yang Jiao (Cornu Saigae Tataricae) powder is an indispensable basic remedy in the treatment of tremor. )上海第二醫(yī)學(xué)院附屬三院用中藥洋金花制劑麻醉時(shí)，意外發(fā)現(xiàn)麻醉后的病人，在2-24日內(nèi)震顫癥狀消失。 (When Yang Jin Hua (Flos Daturae) was used as anaesthetic in the No.3 Hospital of Shanghai the Second Medical College, tremor sym

47、ptoms disappeared in PD patients 2-24 days after anaesthesia.)3、中西醫(yī)結(jié)合治療 Therapy by integrative Chinese and western medicine 對于PD的藥物治療，目前除左旋多巴外，還不斷研制推出了許多新的藥物。各種治療藥物雖能使PD患者的臨床癥狀在一定的時(shí)間內(nèi)獲得一定程度的好轉(zhuǎn)但均不能阻止本病的自然進(jìn)程，且各種藥物都有不同程度的副反應(yīng)，因而限制了其自身在臨床上的應(yīng)用。近年來中西藥聯(lián)合應(yīng)用治療本病，不僅提高了臨床療效，而且大大降低了西藥的用量和副作用。 Besides levodopa, m

48、any novel 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 we

49、stern 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 中藥與美多巴聯(lián)用 TCM combined with madopar 馬龍將臨床觀察病例隨機(jī)分為對照組和治療組。兩組均服用美多巴標(biāo)準(zhǔn)片，根據(jù)病情需要或毒副反應(yīng)適當(dāng)加減調(diào)整劑量。治療組同時(shí)給予中藥熄風(fēng)定顫丸(龜板、制首烏、天麻、白僵蠶、白芍、川芎、石

50、菖蒲等)。對照組給予安慰劑，療程12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 according to the severity of illness and adverse reaction. Patients in treatment group were also given TCM Xifeng Dinchan

51、 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 Paeoniae Alba), Chuan Xiong (Rhizoma Chuanxiong), Shi Chang Pu (Rhizoma Acori Tatarinowii), and so on), while patient

52、s in control group given placebo, and the therapy lasted for 12 weeks. ) 結(jié)果治療組總有效率為90.O明顯高于對照組的62.5：治療組的中醫(yī)癥狀、生存質(zhì)量改善情況明顯優(yōu)于對照組；而治療組藥物毒副癥狀積分較對照組下降更為顯著。證明熄風(fēng)定顫丸合用美多巴治療因服西藥療效衰減并出現(xiàn)明顯毒副反應(yīng)的帕金森病患者，能明顯提高患者生存質(zhì)量，減輕毒副反應(yīng)，增強(qiáng)原有療效。同時(shí)臨床運(yùn)用比較安全。 (The effective rate in treatment group was 90.0%, much higher than that in

53、control group (62.5%); improvement 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 sh

54、owed obvious toxic and adverse 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 中藥與鹽酸舍曲林聯(lián)用 TCM combined with sertraline h

55、ydrochloride 馬云枝等帕金森病伴抑郁狀態(tài)患者隨機(jī)分為治療組，給予柴胡疏肝散(柴胡、白芍、枳殼、陳皮、木香、香附、川芎、炙甘草等)聯(lián)合鹽酸舍曲林片治療，對照組口服鹽酸舍曲林片治療。 (Ma Yunzhi et al. divided the PD patient with depression into two groups randomly. TCM group was given Chaihu Shugan San (Chai Hu (Radix Bupleuri),Bai Shao (Radix Paeoniae Alba), Zhi Qiao (Fructus Auranti

56、i), 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 sertraline hydrochloride orally. ) 結(jié)果治療8周后兩組漢密爾頓抑郁量表(HAMD)評分與治療前相比均有顯著差異(

57、P0.05)；兩組間比較，差異有統(tǒng)計(jì)學(xué)意義(P0.05)；治療后兩組患者中醫(yī)證候積分較治療前下降，觀察組治療后中醫(yī)證候積分較對照組明顯下降(P0.05)。證明柴胡疏肝散加減聯(lián)合鹽酸舍曲林片治療帕金森伴抑郁狀態(tài)療效更優(yōu)于單用舍曲林組。 (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 grou

58、ps also showed significant difference (P 0.05); TCM syndrome score in 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 admi

59、nistration of sertraline hydrochloride.) 四、發(fā)展展望(Prospect)1. 現(xiàn)代醫(yī)學(xué)現(xiàn)有對PD 的藥物治療主要是改善和控制癥狀，但因西藥本身固有的缺陷如長期應(yīng)用療效減退、耐藥及其本身存在的毒副作用等，導(dǎo)致其在臨床上的應(yīng)用有一定的局限性；2. 中醫(yī)藥具有獨(dú)特療效，如可隨證加減、可針對個體調(diào)整用藥、毒副作用較小等；中西醫(yī)結(jié)合用藥，能明顯改善患者的運(yùn)動癥狀和認(rèn)知功能，降低抗PD西藥的用量，減低西藥副作用，改善生活質(zhì)量，降低惡化率。目前還沒有藥物能有效控制PD病程的進(jìn)展。 一）中西醫(yī)結(jié)合多環(huán)節(jié)多靶點(diǎn)干預(yù) Enhancing advantage and avo

60、iding disadvantage through integrative Chinese and western medicine1. 西醫(yī)的優(yōu)勢(Advantages of western medicine) ： 1）針對性強(qiáng)(Targeted) 2）改善癥狀迅速、明顯(Rapid and obvious symptom improvement) 2. 西醫(yī)的不足( Disadvantages of western medicine ) 1）毒副作用大(Strong toxic and adverse effect ) 2）易產(chǎn)生耐藥(Drug resistance) 3）不能從根本上治