神經(jīng)生物學(xué)_緒論

1、神經(jīng)生物學(xué)緒論NEUROBIOLOGYINTRODUCTION韓韓 濟(jì)濟(jì) 生生NeuroscienceExploring the brain 全書分全書分5篇，篇， 24章章 每章：每章： 有目錄，導(dǎo)語(yǔ)有目錄，導(dǎo)語(yǔ) 盡量聯(lián)系生活實(shí)際盡量聯(lián)系生活實(shí)際 有有BOX講解細(xì)節(jié)講解細(xì)節(jié) 有彩圖（光盤）有彩圖（光盤） 章末：有以名詞為綱的回顧章末：有以名詞為綱的回顧 通過(guò)回答問(wèn)題進(jìn)行總結(jié)通過(guò)回答問(wèn)題進(jìn)行總結(jié) 有進(jìn)一步閱讀的資料有進(jìn)一步閱讀的資料 書末有詳盡索引書末有詳盡索引學(xué)習(xí)方法學(xué)習(xí)方法 英語(yǔ)教科書：英語(yǔ)教科書： 是壓力，有后勁是壓力，有后勁 以學(xué)習(xí)名詞為主，要敢于發(fā)音以學(xué)習(xí)名詞為主，要敢于發(fā)音 綜合學(xué)

2、科：綜合學(xué)科：multidisciplinary 以功能為主，結(jié)合形態(tài)以功能為主，結(jié)合形態(tài) 以基礎(chǔ)為主，結(jié)合臨床以基礎(chǔ)為主，結(jié)合臨床教科書內(nèi)容與講課內(nèi)容可能不完全一致，教科書內(nèi)容與講課內(nèi)容可能不完全一致，但鼓勵(lì)看書（教科書），借機(jī)學(xué)習(xí)專業(yè)英語(yǔ)。但鼓勵(lì)看書（教科書），借機(jī)學(xué)習(xí)專業(yè)英語(yǔ)。神經(jīng)科學(xué) (1990-2000 腦的十年) (2001-2100 腦的世紀(jì))生 命 科 學(xué)分子生物學(xué)細(xì)胞生物學(xué) 認(rèn)知科學(xué)開(kāi)發(fā)腦開(kāi)發(fā)人腦 增強(qiáng)智能模擬人腦 智能電腦保護(hù)腦壽命延長(zhǎng) PD, AD, 中風(fēng)高速交通 顱腦, 脊髓外傷生活節(jié)奏 焦慮,抑郁,精神病生活質(zhì)量 鎮(zhèn)痛 祛痛社會(huì)開(kāi)放 吸毒問(wèn)題了解腦分子 細(xì)胞 網(wǎng)絡(luò) 全

3、腦 (離體研究) (無(wú)創(chuàng)在體研究) Patch（電） 腦地形圖 RIA(化學(xué)） PET(化學(xué)） PCR(基因） fMRI (功能） Confocal CT(形態(tài)） (形態(tài)） 行為變化百年來(lái)與神經(jīng)科學(xué)有關(guān)的諾貝爾獎(jiǎng)獲得者選介(I)C.S.Sherrington (英英)18571850190019502000C.Golgi (意意)19261934神經(jīng)元染色方法神經(jīng)元染色方法18431852R.Cajal (西班牙西班牙)“神經(jīng)元學(xué)說(shuō)神經(jīng)元學(xué)說(shuō)”形形態(tài)態(tài)190619521932“突觸”定名“反射”概念“交互”抑制反射學(xué)說(shuō)反射學(xué)說(shuō)生生理理電電生生理理18891977感覺(jué)神經(jīng)纖維電活動(dòng)傳入沖動(dòng)大腦誘

4、發(fā)電位神經(jīng)控制骨骼肌運(yùn)動(dòng)機(jī)制E.D.Adrian (英英)電生理電生理O.Loewi (德德 英英)196118731936（乙酰膽堿）（乙酰膽堿）神經(jīng)化學(xué)神經(jīng)化學(xué)蛙心灌流實(shí)驗(yàn)“迷走物質(zhì)”19681875H.Dale (英英)神經(jīng)末梢分泌乙酰膽堿ACh神經(jīng)化學(xué)神經(jīng)化學(xué)18741965194419631888J.Erlanger (美美)H.S.Gasser (美美)陰極射線示波器神經(jīng)纖維的分類ABC19731881W.R.Hess (瑞士瑞士)腦立體定位儀 hypothalamus方法學(xué)創(chuàng)新方法學(xué)創(chuàng)新1949電生理電生理OxfCambridge徒手切腦片銀染神經(jīng)元染出神經(jīng)末梢，發(fā)現(xiàn)神經(jīng)元之間無(wú)

5、原生質(zhì)聯(lián)系生理科學(xué)進(jìn)展2001，32：187神經(jīng)藥理學(xué)神經(jīng)藥理學(xué)分子藥理學(xué)分子藥理學(xué)百年來(lái)與神經(jīng)科學(xué)有關(guān)的諾貝爾獎(jiǎng)獲得者選介(II)1850190019502000J.C. Eccles (澳大利亞澳大利亞) 191419031963A.L.Hodgkin (英英)B.Katz (德德 英英)1917A.F.Huxley (英英)細(xì)胞內(nèi)微電極突觸后電位抑制性遞質(zhì)突觸突觸電壓鉗技術(shù)動(dòng)作電位的離子學(xué)說(shuō)數(shù)學(xué)方程表述 NM終板電位遞質(zhì)“量子釋放”1911動(dòng)作電位機(jī)制動(dòng)作電位機(jī)制19051983U.Von Euler (瑞典瑞典)交感神經(jīng)遞質(zhì)去甲腎上腺素1970兒茶酚胺代謝影響CAs的藥物電生理電生理1

6、912J.Axelrod (美美)（兒茶酚胺）（兒茶酚胺）神經(jīng)化學(xué)神經(jīng)化學(xué)1913(左右腦左右腦)R.W.Sperry (美美)1981“腦功能側(cè)化腦功能側(cè)化”D.Hubel (加加 美美)19261924T.Wiesel (瑞典瑞典 美美)信信息息加加工工視視皮皮層層E.Neher (德德)1991B.Sakmann (德德)大腦視覺(jué)信息加工視覺(jué)系統(tǒng)發(fā)育的可塑性膜膜片片鉗鉗單單通通道道方方法法學(xué)學(xué)膜片鉗技術(shù)單個(gè)離子通道電流記錄1999英，澳CambridgeCambridgeLevi Montalcini 1986 Nerve growth Factor (NGF) (Italy)百年來(lái)與神

7、經(jīng)科學(xué)有關(guān)的諾貝爾獎(jiǎng)獲得者選介(3)1850190019502000192619232000P.Greengard (美美)1930E.Kandel (美美)A.Carlsson (瑞典瑞典)神經(jīng)系統(tǒng)中的信號(hào)轉(zhuǎn)導(dǎo)蛋白磷酸化蛋白磷酸化慢突觸傳遞慢突觸傳遞多巴胺多巴胺(Schizophrenia)(Parkingsons Disease)(DA)THDC(DA)(cAMP)(PKA)Slow synaptic transmmissionEffects last for seconds to hoursShort term memory lasts for min. to hrsLong term

8、memory lasts for weeksDe novo中中 國(guó)國(guó) 神神 經(jīng)經(jīng) 科科 學(xué)學(xué) 的的 發(fā)發(fā) 展展 開(kāi)開(kāi) 創(chuàng)創(chuàng) 者者: 張錫鈞(協(xié)和), 馮德培(協(xié)和,上海生理所),張香桐(上海生 理所,腦所).兩大事件兩大事件: 1950: 巴甫洛夫“條件反射”學(xué)說(shuō) 1966-1976: “文化革命”期間主要做“針刺麻醉”研究方向研究方向: 痛與鎮(zhèn)痛: 北京: 北醫(yī),中醫(yī)研究院 上海: 上醫(yī)大,中科院生理所, 腦所，神科所 視 覺(jué): 上海: 生理所 北京: 生物物理所 神經(jīng)內(nèi)分泌: 西安: 四軍大 (垂體前葉) 上海: 二軍大 (甾體受體), 北醫(yī)大(神經(jīng)免疫) 其它（發(fā)育，再生，）雜雜 志志:

9、生理學(xué)報(bào)70%論文屬神經(jīng)生理 1927年創(chuàng)刊 (上海生理所) 中國(guó)神經(jīng)科學(xué)雜志 1998年創(chuàng)刊 (上海二軍大) 中國(guó)疼痛醫(yī)學(xué)雜志 1995年創(chuàng)刊 (北醫(yī)大) 中國(guó)神經(jīng)解剖雜志 1985年創(chuàng)刊 (四軍大解剖系）大型專著大型專著: 神經(jīng)科學(xué)綱要 1993年 北醫(yī)大韓濟(jì)生主編 (156萬(wàn)字) 神經(jīng)科學(xué)原理 1999年 北醫(yī)大韓濟(jì)生主編 (200萬(wàn)字)學(xué)學(xué) 會(huì)會(huì): 中國(guó)科學(xué)神經(jīng)學(xué)會(huì) (1994年成立), 1995年會(huì)(上海), 1997年會(huì)(西安),1999年會(huì)(北京), 2001 (香港）研究經(jīng)費(fèi)研究經(jīng)費(fèi): “攀登計(jì)劃”腦功能研究 (1992-1997) 400萬(wàn) 國(guó)家自然科學(xué)基金重大課題2項(xiàng) (神

10、經(jīng)肽,視覺(jué)信息 加工） 200萬(wàn) 國(guó)家自然科學(xué)基金委重點(diǎn)課題12項(xiàng) (每項(xiàng)50-90萬(wàn)) 973項(xiàng)目?jī)身?xiàng)（1999-） （2000萬(wàn)）(3400萬(wàn))差差 距距: 分子神經(jīng)生物學(xué),發(fā)育神經(jīng)生物學(xué)(美國(guó)2.5萬(wàn))(IBRO 3萬(wàn)會(huì)員,1999年以色列)北北 醫(yī)醫(yī) 大大 神神 經(jīng)經(jīng) 科科 學(xué)學(xué) 的的 發(fā)發(fā) 展展神經(jīng)解剖神經(jīng)解剖: 臧玉淦教授, 許鹿希教授 生生 理理: 崔宏, 周佳音， 顧蘊(yùn)輝，于英心北醫(yī)大神經(jīng)北醫(yī)大神經(jīng) 痛與鎮(zhèn)痛 1965- (韓濟(jì)生, 湯健, 任民峰)科學(xué)研究所科學(xué)研究所 海洛因成癮的機(jī)理與治療 1992- (韓濟(jì)生,吳鎏楨) 帕金森氏癥的基因治療 1993- (王曉民,韓濟(jì)生)

11、一院一院 小兒神經(jīng): 癲癇的發(fā)病原理與治療 (吳希如) 神經(jīng)內(nèi)科: 神經(jīng)肌肉病, 腦血管意外, 語(yǔ)言障礙 (陳清棠)六院六院 精神病學(xué): 抑郁癥, 酒精成癮 (沈漁邨)神經(jīng)科學(xué)進(jìn)展 (2000海內(nèi)外中青年)神經(jīng)發(fā)育神經(jīng)發(fā)育,衰老與再生衰老與再生(Neural development, aging and regeneration)18離子通道與突觸傳遞離子通道與突觸傳遞(Ion channels and synaptic transmission)14神經(jīng)系統(tǒng)疾病神經(jīng)系統(tǒng)疾病(Neural diseases, PD,AD, HD, Psych)11感覺(jué)系統(tǒng)感覺(jué)系統(tǒng)(Sensory system

12、, Pain, Visual )7神經(jīng)遞質(zhì)神經(jīng)遞質(zhì),調(diào)質(zhì)調(diào)質(zhì),轉(zhuǎn)運(yùn)體和受體轉(zhuǎn)運(yùn)體和受體(Neurotransmitters, modulators, transporters and receptors, 5-HT, )4神經(jīng)免疫與神經(jīng)內(nèi)分泌(Neuroimmunology and neuroendocrine)新技術(shù)(New technology)2學(xué)習(xí)與記憶(Learning and memory)2運(yùn)動(dòng)系統(tǒng)(Motor system)2 62神經(jīng)發(fā)育與再生神經(jīng)發(fā)育與再生神經(jīng)營(yíng)養(yǎng)因子突觸發(fā)生及 其可塑 性 (蒲慕明,魯白)神經(jīng)細(xì)胞遷移的分子生物學(xué) (饒毅)神經(jīng)干細(xì)胞的應(yīng)用潛力(王偉業(yè))脊髓

13、損傷的修復(fù)(徐小明)視網(wǎng)膜結(jié)細(xì)胞軸突再生(蘇國(guó)輝)視神經(jīng)再生(陳東風(fēng))神經(jīng)移植的免疫學(xué)(段維明)同源盒基因(范明) 離子通道與突觸傳遞離子通道與突觸傳遞離子通道信號(hào)轉(zhuǎn)遞與行為的可塑性(吳春放)KCNQ鉀通道的治療意義(王克威)M通道(王宏聲)超極化離子通道 (俞漢鋼)神經(jīng)細(xì)胞內(nèi)鈣穩(wěn)態(tài)(徐天樂(lè))靜息谷氨酸突觸與神經(jīng)可塑性(卓敏)胞吐的分子機(jī)制(徐濤)神經(jīng)毒(吉永華) 神經(jīng)系統(tǒng)疾病神經(jīng)系統(tǒng)疾病 1.帕金森病 (王曉民) 2.老年癡呆(杜燕生) 3. 亨廷敦病(李曉江) 4. 星型膠質(zhì)細(xì)胞與腦缺氧(于常海)巴甫洛夫：非條件反射巴甫洛夫：非條件反射巴甫洛夫：條件反射巴甫洛夫：條件反射復(fù)雜的復(fù)雜的 操作

14、式條件反射操作式條件反射人的心理活動(dòng)，學(xué)習(xí)記憶，計(jì)算，思維人的心理活動(dòng)，學(xué)習(xí)記憶，計(jì)算，思維 肥肥 胖胖 癥癥能量代謝失衡能量代謝失衡對(duì)美食的渴求對(duì)美食的渴求藥物成癮藥物成癮身體依賴：戒斷癥狀身體依賴：戒斷癥狀精神依賴：心癮精神依賴：心癮痛與鎮(zhèn)痛痛與鎮(zhèn)痛感知功能感知功能情緒反應(yīng)情緒反應(yīng)肥肥 胖胖 癥癥能量代謝失衡能量代謝失衡對(duì)美食的渴求對(duì)美食的渴求藥物成癮藥物成癮身體依賴：戒斷癥狀身體依賴：戒斷癥狀精神依賴：心癮精神依賴：心癮痛與鎮(zhèn)痛痛與鎮(zhèn)痛感知功能感知功能情緒反應(yīng)情緒反應(yīng)疼痛的現(xiàn)代研究方法疼痛的現(xiàn)代研究方法 清醒動(dòng)物神經(jīng)元單位放電 多通道記錄 多通道腦電與腦誘發(fā)電位研究 人體功能磁共振成像(

15、fMRI) Ascending pathways of painDD. Price ，science vol 288，9， June 2000外側(cè)痛覺(jué)系統(tǒng)：外側(cè)痛覺(jué)系統(tǒng)：痛感覺(jué)：背角深層-外側(cè)丘腦-初級(jí)與次級(jí)體感皮層內(nèi)側(cè)痛覺(jué)系統(tǒng)：內(nèi)側(cè)痛覺(jué)系統(tǒng)：痛情緒：背角淺層-內(nèi)側(cè)丘腦-島葉-前扣帶回ABCSchematic drawing of microarrays（微電極芯片）（微電極芯片） Microarrays may be one-, two- or three-dimentional Microwires are grouped together to occupy a target area-

16、10-505100.02.55.07.510.0SI-10-505100.02.55.07.510.0VP外側(cè)通路 the lateral pathway： Contralateral biasIpsilateralContralateralControlSurprise (- ln p)Time (Sec)內(nèi)側(cè)通路 the medial pathway ：Bilateral unbiased response -10-50510ACC0.02.55.07.510.0-10-50510MD0.02.55.07.510.0IpsilateralContralateralControlSurpri

17、se (- ln p)Time (Sec)腦內(nèi)兩套痛覺(jué)編碼體系的功能磁共振(fMRI)測(cè)試 疼痛 感覺(jué)感覺(jué) 與 情緒情緒的可分離性分別加以評(píng)分評(píng)分的可能選擇性地加以干預(yù)干預(yù)Rainville PHypnotic suggestions dissociate pain sensation and pain affectRainville P et al. 1997, Science 277:968-971.Hofbauer RK et al. 2001, J Neurophysiol 86:402-411.不同品系小鼠電針鎮(zhèn)痛效果比較D iffe r e n c e in a n a lg e

18、s ia o f 2 H z E A1 . 0 - 1 . 5 - 2 . 0 m A o n in b r e d s t r a in s o f m ic e129AAKRB6B10B/cC3HC58RIIISSM02 55 07 5n = 1 1 - 2 2S t r a i n sIncrease of Peak %MPE(EA over Control)D iffe r e n c e in a n a lg e s ia o f 1 0 0 H z E A1 . 0 - 1 . 5 - 2 . 0 m A o n in b r e d s t r a in s o f m ic

19、e129AAKRB6B10B/cC3HC58RIIISSM02 55 07 5n = 1 1 - 2 2S t r a i n sIncrease of Peak %MPE(EA over Control)Wan et al. Pain 2001Pain threshold and the effect of 2 Hz EA analgesia in B10 and B6 mice-100102030405060246810EAB10EANSTime（min）TFL（s）-100102030405060246810n = 10EAB6EANSTime（min）TFL（s）1.0-1.5 mAL

20、ow respondersHigh respondersHereditory difference between B6 and B10 mice H9 (chromosome X) Igh2 (chromosome 12) Lv (chromosome 4) Festing, 1992 59-67 cM segment on chromosome 4 McClive et al, 1994 4 loci and 2 segments on chromosomes 2, 11, 13 and 16 Slingsby et al, 1995Pain / analgesia-related gen

21、es in B10 and B6 miceOprd1 OR (Chr 4 64.8 cM)Htr6 5-HT6 R (Chr 4 64.9 cM)Htr1d 5-HT1D R (Chr 4 66.0 cM)Htr1da 5-HT1D R (Chr 4 66.2 cM)Htr1db 5-HT1D R (Chr 4 66.2 cM)Adra1b NA1b R (Chr 11 19.0 cM)Gabra1 GABAA1 R (Chr 11 19.0 cM)Gabrg1 GABAA1 R (Chr 11 19.0 cM)Devi L. A. Oligomerization of Opioid Rece

22、ptors 2002Bioluminesence resonance energy transfer (BRET) technique for testing the distance between two molecules100慢性疼痛的研究韓濟(jì)生韓濟(jì)生 北京大學(xué)神經(jīng)科學(xué)研究所合作者：張張 旭旭 中科院神經(jīng)科學(xué)研究所39830160重點(diǎn)項(xiàng)目結(jié)題驗(yàn)收匯報(bào)2003年2月22-24日Study on Chronic Pain MechanismsGenePeptideProteinIn vitroIn vivoCognitive(DRG) Pain related11 229 ESTNovel

23、GenesOFQNSTEMGDNFMu OR Delta ORIh Ion ChannelHistochem stainingCell culturePatch clampingAcute PainChronic Pain inflammatory neuropathic nerve lesion fMNRPain related brain areasOptimal parametersfor EA treatmentTrends in Neuroscience, 2003; 26: 17-22 Firing RateResponse / ReleaseTransmitterPeptides

24、Thomas Hokfelt, 1991, Neuron 7:867-879經(jīng)典神經(jīng)遞質(zhì)神經(jīng)肽阿阿 片片 肽肽opioid peptides aaYearOpiod receptor電電 針針 (Hz) 腦腦 啡啡 肽肽Enkephalins 51975 + + 2-內(nèi)內(nèi) 啡啡 肽肽-endorphin 311976 + + 2強(qiáng)強(qiáng) 啡啡 肽肽Dynorphins 171979 +100孤孤 啡啡 肽肽Orphanin FQ 17 1995 內(nèi)內(nèi) 嗎嗎 啡啡 肽肽Endomorphins 41997+2Effects produced by EA of different frequencie

25、s2 Hz 100 HzNaloxone reversibility of EA analgesia (ID50, mg/kg) 0.5(mu, delta OR) 20(kappa OR)Induction of the release of neuropeptides in the spinal cordEnk, -EP, EM, GalaninDynorphin, CCK-8Neural pathways revealed by lesion, stimulation, c-fos expression, etc.Arcuate N. hypothalamusParabrachial N

26、.Chronic Inflammatory Pain （炎癥痛）+Neuropathic pain （神經(jīng)源性痛）+Spinal spastic pain （肌痙攣痛）0+0281624485d0102030hrcontrolneedling2 Hz100 Hzn=11-12*Time after EANumber of Paw Lifts from cold plate/ 5 minThe Cumulative Effect of Electroacupuncture on Cold-induced Neuropathic Pain3735Hzm m2 15 100EM / ENK /EP

27、d d DYNAntinociception andTreatment of drug addictionFrequency of electroacupunctureNeuropeptides released in CNSOpioid receptorsPhysiological and therapeutic effectsNeurochemical Basis of Acupuncture EffectsDREAMPeptide released in CNSEnkDynEnk + DynAB2 Hz2 Hz100 Hz100 Hz30691215 s2 Hz100 Hz Hamza,

28、 M.A. et al. (1999) Effect of the frequency of transcutaneous electrical nerve stimulation on the postoperative opioid analgesic requirement and recovery profile. Anesthesiology 91, 1232-8 Wang, B.G. et al. (1997) Effect of the intensity of transcutaneous acupoint electrical stimulation on the posto

29、perative analgesic requirement. Anesth. Analg. 85, 406-13 El-sayed, A. et al. (1999) Percutaneous electrical nerve stimulation for low back pain. A randomized crossover study. JAMA 281, 818-823 Hamza, M.A. et al. (1999) Effect of the duration of electrical stimulation on the analgesic response in pa

30、tients with low back pain. Anesthesiology 91, 1622-7 Hamza, M.A., et al. (2000) Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. Diabetic Care 23, 365-370實(shí)驗(yàn)研究結(jié)果的實(shí)驗(yàn)研究結(jié)果的 臨床驗(yàn)證臨床驗(yàn)證 Clinical verification of basic research11Nerve pathways for low and hig

31、h frequency EA analgesia 100 Hz 2 Hz -endEnkDynPBNArcuate N.Hypoth.PAGMedullaDHN0255075100125150-2.50.02.55.07.5Time (s)Signal Intensity (%)R. Primary Motor Area (R-MI)R. Supplementary Motor Area (R-SMA)020406080100120-2.50.02.55.07.5Time (s)Signal Intensity (%)02550751001250.000.250.500.751.00p0.00

32、1% change of pain threshold (radiantheat withdrawal)Correlation Coefficient02550751001250.000.250.500.75p0.01% change of pain threshold (radiantheat withdrawal)Correlation Coefficient Brain areas involved in AA: fMRI studies in humansPositive correlation43 41R. Hippocampus (R-Hi)L. Hippocampus (L-Hi

33、)020406080100120-2.50.02.55.07.5Time (s)Signal Intensity (%)020406080100120-2.50.02.55.07.5Time (s)Signal Intensity (%)0255075100125-0.75-0.50-0.250.00p0.01% change of pain threshold (radiantheat withdrawal)Correlation Coefficient0255075100125-0.75-0.50-0.250.000.25p0.05% change of pain threshold (r

34、adiantheat withdrawal)Correlation Coefficient44Brain areas involved in AA: fMRI studies in humansNegative correlation4202550751001250.000.250.500.751.00r2=0.8879p=0.0001change of pain threshold (%)Correlation CoefficientR-MI02550751001250.000.250.500.750.78110.0016r2=p =change of pain threshold (%)C

35、orrelation CoefficientR-SMA02550751001250.000.250.500.750.60540.0135r2=p =change of pain threshold (%)Correlation CoefficientR-SII02550751001250.000.250.500.75r2=0.76650.0020p =change of pain threshold (%)Correlation CoefficientL-SII02550751001250.000.250.500.750.66980.0070r2=p =change of pain thres

36、hold (%)Correlation CoefficientL-Ins02550751001250.000.250.500.75r2=0.8151p =0.0009change of pain threshold (%)Correlation CoefficientR-BA2402550751001250.000.250.500.750.85730.0010r2=p =change of pain threshold (%)Correlation CoefficientR-Th02550751001250.000.250.500.75r2=0.8250p =0.0007change of p

37、ain threshold (%)Correlation CoefficientL-STG0255075100125-0.75-0.50-0.250.000.250.64470.0164r2=p =change of pain threshold (%)Correlation CoefficientR-Hi0255075100125-0.75-0.50-0.250.00r2=0.6693p =0.0070change of pain threshold (%)Correlation CoefficientL-Hi02550751001250.000.250.500.750.28700.1371

38、r2=p=change of pain threshold (%)Correlation CoefficientR-SI02550751001250.000.250.500.750.16410.2795r2=p =R-Inschange of pain threshold (%)Correlation CoefficientRight Primary Motor AreaRight Supplementary Motor AreaLeft Secondary Somatosensory AreaLeft InsulaRight Secondary Somatosensory AreaLeft

39、Superior Temporal GyrusRight ThalamusRight Anterior Cingulate CortexRight HippocampusRight HippocampusRight Primary Somatosensory AreaRight InsulaEffects of 2 Hz EA on the brain fMRI SummaryBrain Areas2 Hz100 HzR-Sensory II+L-Sensory II+R-Broadman Area 24+R-Thalamus+L-Insular+R-Primary Motor Area+R-

40、Supplementory MA+L-Superior Temporal Gyrus+R-Broadman Area 40+L-Broadman Area 24+L-Nucleus Accumbens+PONS+R-Hippocampus-L-Hippocampus -R-Amygdala-肥肥 胖胖 癥癥能量代謝失衡能量代謝失衡對(duì)美食的渴求對(duì)美食的渴求藥物成癮藥物成癮身體依賴：戒斷癥狀身體依賴：戒斷癥狀精神依賴：心癮精神依賴：心癮痛與鎮(zhèn)痛痛與鎮(zhèn)痛感知功能感知功能情緒反應(yīng)情緒反應(yīng)7255786100010203040506070809010019901993199720002002 Heroi

41、n addicts in China (ten thousand)80% - 85% heroin addictsHeroin addiction:can acupuncture help?針刺是否能戒除海洛因成癮？H.A.N.SHans Acupoint Nerve Stimulator (HANS)韓韓 氏氏 穴穴 位位 神神 經(jīng)經(jīng) 刺刺 激激 儀儀Threshold (mA) of afferent fibers activated by EA (HANS) at different frequenciesA012345672 Hz0.6 ms15 Hz0.3 ms100 Hz0.2 m

42、sTypes of nerve fibers* Threshold of excitation (mA)AACEffect of HANS on heart rate of heroin addictsDay of treatment1234567891060708090100110120130Control2 Hz2/100 Hz100 Hzn=13-16*Heart Rate (beat/min)Body Weight (kg)01234567891011Days of Treatment45505560Control2Hz2/100Hz100Hz(n=26-32)Effect of HA

43、NS on Body Weight during Opiate Withdrawal*CRAVING: the most difficult issue一朝吸毒，終身想毒。The auto-track conditioned place preference (CPP) instrumentMorphine-induced conditioned place preference (CPP)Dose-dependent effect00.01 0.03 0.10.31.03.0 10.00.000.250.500.75* *n=9-12Mor ( mg/kg )*p0.05, *p0.01,

44、*p 100 Hz100 Hz 2 HzElectroacupuncture treatment for drug addictionVTAOpiateGABANAcDADATCocaineEuphoriaEnkDynElectroacupuncture2 Hz100 HzPresynaptic inhibitionSubstitutionA100 bp2000 bp1000 bp750 bp500 bp250 bpDL 2000 NSCPP2 Hz100 HzrestrainGAPDH (532 bp)PPD (250 bp)Effect of 100Hz EA on the level o

45、f PPD mRNA in NAc of CPP rats B0.00.51.01.5Grey scale ratios(PPD/GAPDH)Treatment*#n=4NSCPP2 Hz100 HzrestrainEffect of 2Hz EA on the level of PPE mRNA in NAc of CPP rats Grey scale ratios(PPE/GAPDH)0.000.250.500.751.00NSCPP*#2 Hz100 Hzrestrainn=42000 bp1000 bp750 bp500 bp250 bp100 bpDL2000CPP2 Hz100

46、HzrestrainGAPDH（532 bp）PPE（402 bp）NS美國(guó)權(quán)威性美國(guó)權(quán)威性“物質(zhì)濫用物質(zhì)濫用”教科書教科書Joyce Lowinson 等主編等主編第第4版，版，2004“針刺戒毒針刺戒毒”一章一章由韓濟(jì)生編寫由韓濟(jì)生編寫肥肥 胖胖 癥癥能量代謝失衡能量代謝失衡對(duì)美食的渴求對(duì)美食的渴求藥物成癮藥物成癮身體依賴：戒斷癥狀身體依賴：戒斷癥狀精神依賴：心癮精神依賴：心癮痛與鎮(zhèn)痛痛與鎮(zhèn)痛感知功能感知功能情緒反應(yīng)情緒反應(yīng)肥胖的發(fā)展趨勢(shì)肥胖的發(fā)展趨勢(shì)肥胖發(fā)病機(jī)理肥胖發(fā)病機(jī)理GenesEnvironmental factors HANSHANS治療肥胖癥：人體研究結(jié)果治療肥胖癥：人體研究結(jié)

47、果048121620242832-4-3-2-10 A HANS B C HANS Dn=16Time ( week )ABCD-4-3-2-10*HANS ( 3 time / week )Change of body weight ( kg )梁門，一對(duì)。天樞，一對(duì)。水道，一對(duì)。梁丘，公孫。頻率：2/100 Hz每周3次每次30 分鐘 大鼠實(shí)驗(yàn)結(jié)果（高能食物引起肥胖）大鼠實(shí)驗(yàn)結(jié)果（高能食物引起肥胖） Diet-induced Obesity (DIO) After 14 weeks02468101214160100200300400500600700High energy diet (n =80)Normal diet (n =20)*Time (week)Body weight (