第40卷第3期解剖學(xué)報(bào)Vol 40, No. 3200年6月ACTA ANATOMICA SINICAJun.2009·395乙醇對(duì)大鼠腦內(nèi)5HT能神經(jīng)體系的影響李雙成12康云霄!石葛明1“崔慧先2王磊2李學(xué)平(1.河北醫(yī)科大學(xué)神經(jīng)生物學(xué)研究室;2.河北醫(yī)科大學(xué)解剖學(xué)教研室,石家莊050017[摘要]目的觀察乙醇處理大鼠腦內(nèi)色氨酸羥化酶(TPH)、5羥色胺(5Hr)和5羥色胺轉(zhuǎn)運(yùn)體(sERT)的表達(dá)改變判斷乙醇對(duì)腦內(nèi)5HT能神經(jīng)體系的影響。方法以20%乙醇代替飲水飼養(yǎng)30只Wisr大鼠6個(gè)月;利用免疫組織化學(xué)、免疫印跡及流式細(xì)胞術(shù)等方法,分析乙醇處理大鼠有關(guān)腦區(qū)5HT能神經(jīng)體系相關(guān)指標(biāo)的改變。結(jié)果1.免疫組織化學(xué)法可見,乙醇處理組大鼠腦內(nèi)中縫背核TH5H免疫反應(yīng)陽性神經(jīng)元數(shù)量少于對(duì)照組(P<00);TH免疫陽性神經(jīng)元直徑小于對(duì)照組(P<001);相關(guān)腦區(qū)TPH5-H和SERT免疫反應(yīng)灰度值比對(duì)照組增高(P<0.05)。2.流式細(xì)胞術(shù)檢測(cè)可見,乙醇處理組大鼠TPH、5HT和SERT的表達(dá)量低于對(duì)照組(P<0.05)。免疫印跡法檢測(cè)可見乙醇處理組大鼠SERT和TPH與actn相對(duì)吸光度比值均小于相應(yīng)對(duì)照組(P<0.05)。結(jié)論乙醇降低腦內(nèi)TP5-HT和SERT的表達(dá),可能改變腦內(nèi)5HT能神經(jīng)體系的功能活動(dòng)[關(guān)鍵詞]乙醇;色氨酸羥化酶;5羥色胺;5-羥色胺轉(zhuǎn)運(yùn)體;免疫組織化學(xué);流式細(xì)胞術(shù);免疫印跡法;大鼠[中圖分類號(hào)]Q952.4[文獻(xiàn)標(biāo)志碼]A[Do10.3969/j,in,05291356.2009.03.010Effect of ethanol on the serotonergic systems in rat brainL Shuang-cheng",Kang Yun-xiao, SHI Ge-ming", CUI Hui-xian, WANG Lei, LI Xue-ping(I. Department of Neurobiology: 2. Department of Anatomy Hebei Medical University, Shijiazhuang 050017, China)[Abstract] Objective To study the effect of ethonal on the serotonergic systems by analyzing the altered expression oftryptophan hydroxylase(TPH), serotonin(5-HT)and serotonin transporter( SERT)in the brain of ethanol-treated rats. MethodsWistar rats were treated with 20% ethanol for 6 months. Immunocytochemistry, flow cytometry and Westem blotting were usedto analyze the altered expression of the serotonergic markers in different brain regions of the ethanol-treated rats. Resultsmistry showed the number of TPH or 5-Ht positive neurons in dorsal raphe nucleus( DRN)is leas in ethanol.treated rats than that in control(P<0.01), the diameter of TPHin dRN is smaller than that in control(P<0.01)andthe mean gray value of tpH, 5-ht and SERT in observed regions of the ethanol-treated rats is larger than that in control (P<0.05).2. Flow cytometry showed the expression of TPH, 5-HT and SERT in the studied regions of the ethanol-treated ratsdecreased significantly compared with control(P<0.05).3. Westem blotting showed the ratio of SERT/B-actinin or TPH/B-actinin in analyzed regions of the ethanol-treated rats is smaller than that in control(P <0.05). Conclusion Ethanol decreasesthe expression of TPH, 5-HT and SERT of rat brain, which may result in the altered activity of serotonergic systemsKey words] Ethanol; Tryptophan hydroxylase; Serotonin; Serottometry; Western blotting: Rat近年有關(guān)酗酒對(duì)腦內(nèi)5-羥色胺(5T)能神經(jīng)基有關(guān)。為進(jìn)一步確定酗酒對(duì)腦內(nèi)5HT能神經(jīng)體系影響的研究主要集中于觀察腦內(nèi)5羥色胺轉(zhuǎn)運(yùn)體系的影響本研究利用免疫組織化學(xué)法、免疫印跡體( serotonin transporter,sERT)結(jié)合信號(hào)的改變“,法以及流式細(xì)胞術(shù)等觀察乙醇處理大鼠有關(guān)腦區(qū)5但所獲結(jié)果并不一致。表現(xiàn)為降低36無變H能神經(jīng)體系的不同指標(biāo)、特別是SERT蛋白的改化甚至增高,這很可能與所觀察的酗酒個(gè)體例變,從而判斷乙醇對(duì)腦內(nèi)5H能神經(jīng)體系的影響。數(shù)少、酗酒并發(fā)癥各異以及缺乏SET特異性配材料和方法[收稿日期]2008-01403[修回日期]2003031.動(dòng)物模型基金項(xiàng)目]河北省教育廳計(jì)劃攻關(guān)項(xiàng)目資助(2007129);河北60只(河北醫(yī)省科學(xué)技術(shù)研究與發(fā)展指導(dǎo)課題資助項(xiàng)目科大H中國煤化為對(duì)照組和乙醇作者藺介]李雙成(1971-),男(漢族),河北省石家莊市人,處理CNMHG大鼠參照More醫(yī)學(xué)博士,副教授等的方法每天以20%乙醇代替飲水,每只實(shí)驗(yàn)動(dòng)物通訊作者( To whom correspondence should be addressed)每日飲入20%乙醇量為(1642±1.35)ml。飼養(yǎng)6E-mail:shigml23@126.comTel:(0311)86265503個(gè)月后處死。396解剖學(xué)報(bào)40卷,3期2.實(shí)驗(yàn)方法隆抗體(1:500),4℃過夜。PVDF膜以TTBs洗32.1免疫組織化學(xué)染色:大鼠于深麻醉下次,每次10min。洗膜后加HRP標(biāo)記的羊抗兔或小40g/L多聚甲醛(4℃)經(jīng)心灌注固定h,取腦置相同鼠g(1:500037℃孵育1.5h。TTBs洗膜(3次,固定液后固定4h,300gL蔗糖液4℃過夜。所需部10min/次),TBS洗膜1次。增強(qiáng)型化學(xué)發(fā)光試劑位行冠狀位冷凍連續(xù)切片(厚40m),間斷集片,PB(ECL)增強(qiáng)化學(xué)發(fā)光后入X線片暗盒曝光,顯影洗片后行免疫組織化學(xué)反應(yīng)。相關(guān)切片分別以小鼠定影。底片透掃,用 Lab Works45軟件測(cè)量免疫印抗色氨酸羥化酶( try tophan hydroxylase,TPH)單克隆跡條帶相對(duì)吸光度值,計(jì)算與內(nèi)參免疫印跡條帶相抗體(1:100,Sigm公司)、兔抗5-HT多克隆抗體對(duì)吸光度值的比值,進(jìn)行分析。(尾殼核1:50、腦干1:800,sigm公司)兔抗2.4統(tǒng)計(jì)學(xué)方法:所得上述相關(guān)數(shù)據(jù)以均值±標(biāo)SERT多克隆抗體(1:1000,1 mmunostar公司)4℃孵準(zhǔn)差(x±s)表示,經(jīng)方差齊性檢驗(yàn)后發(fā)現(xiàn),該資料育48h;依一抗種屬以生物素化羊抗小鼠lgG(1:服從正態(tài)分布且方差齊行成組設(shè)計(jì)的t檢驗(yàn),P<500)或羊抗兔lgC(1:500)室溫孵育切片2h,1:5000.05為差異具有統(tǒng)計(jì)學(xué)意義。HRP鏈霉卵白素室溫孵育1h。每步間以TBs洗片DAB呈色、貼片、封片、觀察。用100g/L正常羊血清結(jié)果代替一抗,相同步驟孵育,作為陰性對(duì)照免疫組織化學(xué)結(jié)果細(xì)胞計(jì)數(shù):40倍物鏡下,參照 James等的方法,般觀察發(fā)現(xiàn),乙醇處理組大鼠中縫背核(B7)按 Paxinos大鼠腦圖譜,分別計(jì)數(shù)中縫背核(B7)lcm2TPH、5-HT以及SERT免疫反應(yīng)強(qiáng)度比對(duì)照組減弱面積中TPH和5HT免疫反應(yīng)陽性神經(jīng)元數(shù)量。(圖1A,1B,2A,2B,3A,3B)。TPH5HT免疫反應(yīng)細(xì)胞直徑:40倍物鏡下,參考 James等的方法,選陽性細(xì)胞數(shù)量少于對(duì)照組(1A,1B,2A,2B);高倍取中縫背核胞核明顯、無重疊的TPH陽性神經(jīng)元,測(cè)鏡下,乙醇處理組大鼠中縫背核、尾殼核、隔核以及量其最長徑及最短徑,取平均值作為細(xì)胞直徑。扣帶皮質(zhì)SERT陽性纖維比對(duì)照組稀疏(3A,3B,灰度測(cè)量: HPIAS-1000圖文系統(tǒng)分析乙醇處理4A,4B,5A,5B)。和對(duì)照組中縫背核(B7)(TPH5-HT和SERT)、尾細(xì)胞計(jì)數(shù)顯示,與對(duì)照組相比,乙醇處理組中縫殼核(5H和SET)、隔核、扣帶皮質(zhì)(SERT)的5HT背核TPH、T免疫反應(yīng)陽性神經(jīng)元數(shù)量明顯減能神經(jīng)元有關(guān)指標(biāo)的灰度值。TPH、5T和SERT少,減少程度分別達(dá)到3564%和35.33%(P<的表達(dá)強(qiáng)度與測(cè)得灰度值負(fù)相關(guān)。0.01,表1)。細(xì)胞直徑測(cè)量顯示,與對(duì)照組相比,乙2.2流式細(xì)胞術(shù)檢測(cè):大鼠快速斷頭取腦冰板醇處理組中縫背核背側(cè)部和腹側(cè)部TPH陽性神經(jīng)上取所需腦組織,制備單細(xì)胞懸液并取1x10/m細(xì)元直徑減小程度達(dá)569%、腹外側(cè)部達(dá)861%(P胞,分別加入小鼠抗TPH單克隆抗體、兔抗SERT多<0.01,表1)克隆抗體及兔抗5-HT多克隆抗體各0.1ml(1:100灰度測(cè)量顯示,與對(duì)照組相比,乙醇處理組各指室溫孵育30min,人PBs1oml洗滌,離心棄上清,入標(biāo)灰度值均有增高。其中TPH在中縫背核(B7)增異硫氫熒光素免疫球蛋白G(FmCG)及藻紅素免高幅度達(dá)19.91%(P<0.05,表2);5H在中縫背疫球蛋白G(PE1c)0.1ml避光室溫孵育30min,加核(B7)和尾殼核的灰度值分別增高了30.47%和入PBs1ml離心,棄上清,PBS0.1ml經(jīng)500目銅10.05%(P<0.05,表2);SERT在中縫背核(B)、扣網(wǎng)過濾上機(jī)檢測(cè),對(duì)蛋白免疫熒光標(biāo)記物測(cè)定時(shí)設(shè)帶皮質(zhì)尾殼核和隔核的增加也分別達(dá)到16.30%、一抗或二抗的本底對(duì)照和陰性對(duì)照。電腦記錄,分0.45%、19.17%和357%(P<0.05,表2別計(jì)數(shù)乙醇處理組和對(duì)照組TPH、5-H和SERT的2.流式細(xì)胞術(shù)檢測(cè)表達(dá)量 X-mode值,所得結(jié)果轉(zhuǎn)變成線性數(shù)據(jù),取log乙醇處理組TPH、5-HT和SERT的表達(dá)量與對(duì)( X-mode)×340。照組相比減少,比各自相應(yīng)的對(duì)照組分別減少了23免疫印跡法檢測(cè):大鼠快速斷頭取腦,冰板68%、13.88%和73%(P<0.05,表3,圖6)。上取上下丘腦之間的腦組織入液氮速凍后入低溫冰3.免疫印跡檢測(cè)箱備用。取所需腦組織入4℃裂解液勻漿5min,冰中國煤化工與Bm免疫浴靜置1h,4℃離心,取上清, Bradford法測(cè)定蛋白濃印帶皮質(zhì)、尾殼核和中度。每個(gè)樣品取50總蛋白經(jīng)100g/ L SDS-PAGE縫CNMHG76%(P<005,表凝膠電泳分離,電轉(zhuǎn)移至硝酸纖維素(PVDF)膜上,4,圖7);而中縫背核的TPH與 B-actin條帶相對(duì)吸光用50g/L脫脂奶粉室溫封閉2h,分別入50g/L脫脂度比值則減少了141%(P<005,表4圖8)奶粉稀釋的小鼠TPH單克隆抗體和兔抗SERT多克Vol, 40, No. 3李雙成等.乙醇對(duì)大鼠腦內(nèi)5H能神經(jīng)體系的影響397圖1A免疫組織化學(xué)法示對(duì)照組大鼠中縫背核TPH免疫反應(yīng)。ABC法染色,DAB顯色(下同)x16圖1B免疫組織化學(xué)法示乙醇處理組大鼠中縫背核TPH免疫反應(yīng)。x16圖2A免疫組織化學(xué)法示對(duì)照組大鼠中縫圖2B免疫組織化學(xué)法示乙醇處理組大鼠1A1B中縫背核5HT免疫反應(yīng)。x圖3A免疫組織化學(xué)法示對(duì)照組大鼠中縫背核SERT免疫反應(yīng)。x13.2圖3B免疫組織化學(xué)法示乙醇處理組大鼠中縫背核SERT免疫反應(yīng)圖4A免疫組織化學(xué)法示對(duì)照組大鼠尾殼核SERT免疫反應(yīng)2A2B圖4B免疫組織化學(xué)法示乙醇處理組大鼠尾殼核SERT免疫反應(yīng)。x50圖5A免疫組織化學(xué)法示對(duì)照組大鼠隔核sERT免疫反應(yīng)圖5B免疫組織化學(xué)法示乙醇處理組大鼠隔核SERT免疫反應(yīng)ABC. DAB3A3B Fig 1B TPH immunoreactivity in the drn ofFig- 2A 5-HT immunoreactivity in the dRn ofcontrol group using the method ofFig2B 5HTeactivity in the drn ofethanol treated group using the method4Bof ABC. DABFig 3A SERT imrctivity in the DRN ofcontrol group using the methodABC. DAB staFig 3B SERT immunoreactivity in the drn ofethanol treated group using the meFig 4A SERT immunoreactivity in theCaudate-Putamen CPu)of control5A5Bgroup using the method of ABC. DABFig 4B SERT immunoreactivity in the CPu of ethanol treated group using the method ofFig 5A SERT immunoreactivity in the septal nucleus of control group using the method of ABC. DAB stain x50Fig5B SERT immunoreactivity in the septal nucleus of ethanol treated group using the method of ABC. DAB stain x50表1乙醇處理大鼠腦內(nèi)5H能神經(jīng)元的變化(均值±標(biāo)準(zhǔn)差)Table 1 The changes of of 5-HT energic neurons in ethanol-treated group(i+ s)5羥色胺(5-HT)色氨酸羥化酶(TPH)分組數(shù)目(個(gè)cm2)( number)數(shù)目(個(gè)/cm2)( number)直徑( diameter,pm)中縫背核(DRN)中縫背核(DRN中國煤化工腹外側(cè)部(Dv對(duì)照組( control24.57:0.7024.86±1.28乙醇處理組( ethanol)CNMHG 11.84+1.5015.89±0.6716.00±1.0010.82±1,69與對(duì)照組比較( Compared with control group)P<0.01398解學(xué)報(bào)40卷,3期表2乙醇處理組大鼠腦內(nèi)相關(guān)腦區(qū)TPH5H和SERT的灰度比較(均值±標(biāo)準(zhǔn)差)Table 2 The comparison of the mean gray scale value of TPH, 5-HT and SERT in ethanol-treated group(i t s)色氨酸羥化酶TPH5羥色胺5HT5羥色胺轉(zhuǎn)運(yùn)體SERT分組中背縫核尾殼核中縫背核尾殼核中背縫核扣帶皮質(zhì)DRN8880±1.29164.94±1.844578±543102.68±7.72109.57±280149.44±14.16118.16±8.13乙醇處理組( ethano)106.48±681.52±2.4549.73±1.67122.36±754·120.45±665·180.00±1.85·157.83±9.46與對(duì)照組比較( Compared with control group)“P<0.01;P<0.05表3流式細(xì)胞術(shù)檢測(cè)大鼠中縫背核TH5HT和SERT的表達(dá)變化(均值±標(biāo)準(zhǔn)差)Table 3 The altered expression of TPH, 5-HT and SERT in DRN of rat by flow cytometry(i t s)分組(goup)色氨酸羥化酶(TPH)5羥色胺(5-HT)5羥色胺轉(zhuǎn)運(yùn)體(SERT)對(duì)照組( contro)638.30±1.37439.2±19.99553.36±1513乙醇處理組( ethanol)595,20±13.5378.25±6,84513.11±12.05與對(duì)照組比較( Compared with control group)“P<0.05函10101021010°101021010°10102103FL2 LOGFL2 LOG相對(duì)含量( relative contaet相對(duì)含量( relative contaet相對(duì)含量( relative contrnet)1010101010°1010210≤10°1010210FL2 LOGFLI LOGFL2 LOG相對(duì)含量( relative contract)相對(duì)含量( relative contaet)相對(duì)含量( relative contaet)5-羥色胺(5-H色氨酸羥化酶(TPHD5-羥色胺轉(zhuǎn)運(yùn)體(SERT)圖6流式細(xì)胞術(shù)檢測(cè)乙醇處理組大鼠中縫背核5 HT. TPH和SERT的表達(dá)變化Fig.6 The expression of 5-Hr, TPH and SERT in DRN o brain rat by flow cytometry表4免疫印跡法檢測(cè)乙醇處理大鼠腦內(nèi)SERT和TPH的表達(dá)變化(比值均值±標(biāo)準(zhǔn)差)Table 4 The altered expression of SERT and TPH in ethanol-treated group(Ratio, i t s)分組色氨酸羥化酶(TPH)5羥色胺轉(zhuǎn)運(yùn)體(SERT)中縫背核(DRN)中縫背核(DRN尾殼核(cPu)扣帶皮質(zhì)(對(duì)照組( control)00064±1.13×10-4037:1.310-30.004:8.97×10-0.034±5.6乙醇處理組( ethanol0.0055±6.17X100.0034±1.53×10*0.002:1.35×100031:6.9×10與對(duì)照組比較( Compared with control group)“P<0.01ContreEthanol中國煤化工NMHG圖7免疫印跡檢測(cè)乙醇對(duì)大鼠扣帶皮質(zhì)、尾殼核和中縫背核SERT表達(dá)的影響d ehanol on SERtin Cingulate gyrus(Cg), CPu andVol 40, No. 3李雙成等乙醇對(duì)大鼠腦內(nèi)5H能神經(jīng)體系的影響399進(jìn)一步的研究證實(shí)。Control以往的研究表明腦內(nèi)5H能上行投射纖維主要來自腦干中縫核群頭側(cè)組,其中中縫背核是最重要的5H能神經(jīng)核團(tuán),與前腦如大腦皮質(zhì)海馬等諸多腦區(qū)具有廣泛的投射聯(lián)系。5-H受體具有多圖8免疫印跡法檢測(cè)乙醇處理對(duì)大鼠中縫背核TPH種亞型,參與腦內(nèi)多種神經(jīng)活動(dòng),如情感、認(rèn)知及睡表達(dá)的影響眠等的調(diào)控。酗酒者6或酗酒人腦標(biāo)本3sERTFig. 8 The effect of Ethanol on TPin drn of結(jié)合信號(hào)的減弱,以及我們?cè)陂L期攝入乙醇大鼠腦內(nèi)所發(fā)現(xiàn)的5H能神經(jīng)體系多個(gè)指標(biāo)降低,表明長討論期攝入乙醇導(dǎo)致了5HT能神經(jīng)體系功能活動(dòng)的障礙,從而可能影響腦內(nèi)5HT能神經(jīng)體系所參與的功限速酶TPH決定神經(jīng)遞質(zhì)5I的合成效率,位能活動(dòng)。于5HT能神經(jīng)末梢的膜蛋白SERT則通過再攝取突近年對(duì)酗酒者腦內(nèi)是否存在5HT神經(jīng)體系改觸間隙的5H而中止其對(duì)突觸后神經(jīng)元的作用。變的研究主要以配基放射自顯影術(shù)檢測(cè)酗酒人腦標(biāo)SERT既是反應(yīng)5H能神經(jīng)元功能活動(dòng)的重要指本、以 CIT PET/SPECT配基顯像技術(shù)檢測(cè)酗酒者腦標(biāo),也是反應(yīng)5H能神經(jīng)末梢多寡的敏感指內(nèi)的SERT結(jié)合信號(hào)變化,這些研究由于檢測(cè)的只標(biāo)。SET和TPH的表達(dá)變化都將直接影響5H是單一指標(biāo)的改變,而SET蛋白表達(dá)受多種因素能神經(jīng)元參與的神經(jīng)活動(dòng)。本研究通過對(duì)大鼠5HT的影響除與個(gè)體的遺傳背景有關(guān)外“m,死后取材能神經(jīng)元的免疫組織化學(xué)、免疫印跡以及流式細(xì)胞術(shù)的時(shí)間以及伴發(fā)疾病都可能影響SERT表達(dá)變化;結(jié)果的分析發(fā)現(xiàn),乙醇處理引起腦內(nèi)5HT能神經(jīng)體另外,配基顯像技術(shù)所用配基PCr,并非只結(jié)合系多個(gè)指標(biāo)的降低。我們發(fā)現(xiàn),無論是5-Ⅲ能神經(jīng)SERT,有研究發(fā)現(xiàn),βCT除結(jié)合SERT還能結(jié)合多元投射源區(qū)(中縫背核B7),還是其投射靶區(qū)(尾殼巴胺轉(zhuǎn)運(yùn)體( dopamine transporter,DAT)",而多數(shù)腦核扣帶皮質(zhì)及隔核)SET的表達(dá)均顯著減弱。這與區(qū)都有SERT和DAT的交織分布,因此,應(yīng)用pcr近年應(yīng)用配基放射自顯影技術(shù)發(fā)現(xiàn)酗酒人腦標(biāo)本杏配基顯像技術(shù)難以確定SERT在酗酒者腦內(nèi)的真實(shí)仁核和尾狀核SET結(jié)合信號(hào)減少-,應(yīng)用配基顯水平。同時(shí)酌酒還可能引起DAT的表達(dá)改變而混像技術(shù)發(fā)現(xiàn)酗酒者SERT標(biāo)記信號(hào)顯著降低以及淆SERT變化的真實(shí)本質(zhì),這些都可能是造成目前免疫放射自顯影發(fā)現(xiàn)SERT表達(dá)減少的結(jié)果一研究報(bào)道結(jié)果不完全一致的原因。本研究采用致。SERT在所觀察腦區(qū)的低標(biāo)記信號(hào)的結(jié)果表明,SERT特異性抗體識(shí)別抗原的方法,檢測(cè)的是組織內(nèi)長期攝入乙醇可能干擾了5H能神經(jīng)元的代謝活蛋白的含量高低,真實(shí)地反映了腦內(nèi)SERT含量的動(dòng)降低了SERT蛋白的表達(dá)。我們應(yīng)用免疫組織化改變,并從多個(gè)方面觀察到腦內(nèi)5H能神經(jīng)體系的學(xué)免疫印跡以及流式細(xì)胞術(shù)在乙醇處理組大鼠5-變化,為酗酒引起腦內(nèi)5H能神經(jīng)活動(dòng)的障礙提供HT能神經(jīng)元投射源區(qū)所觀察到的TPH低表達(dá)以及其了直接的形態(tài)學(xué)依據(jù)反應(yīng)產(chǎn)物5H在中縫背核、尾殼核降低的結(jié)果更進(jìn)參考文獻(xiàn)步說明長期攝人乙醇可能導(dǎo)致5HT能神經(jīng)體系【1Mmr,mphE,HB,A. Serotonin transporter distribution功能活動(dòng)的減弱。本研究在乙醇處理大鼠所觀察到o alcoholic and nonalcoholic的SET、TPH以及5H的減少推測(cè)可能是乙醇處理companion糾lct: a whole-hemisphere autoradiog-y時(shí)[刀的毒性作用引起了大鼠腦內(nèi)5-HT能神經(jīng)元的變性所Am J Psychiatry,2002,159(4):599606,致。近年的研究發(fā)現(xiàn)長期乙醇處理可引起小腦普肯2】sokM, Thienen J, Haukijavi T,l. Amygdala Serotonin耶細(xì)胞樹突內(nèi)滑面內(nèi)質(zhì)網(wǎng)擴(kuò)張,且部分這樣的樹突出Transporters in alcoholics measured by wholehemisphere autoradiography刀]. Synapse,200,61(8現(xiàn)衰老和缺氧過程中常見的變性體( degenerating【3 STorvik M, Tiihonen J, Haukijavi T,l. Lower serotonin transporterbodie)y,這些改變可能與神經(jīng)元的內(nèi)在特性有關(guān)同樣的動(dòng)物模型小腦顆粒細(xì)胞則無類似的超微結(jié)[4] Brown aK,CDr, Fujita M, et al.rr["c] DASB imaging構(gòu)變化。盡管在普肯耶細(xì)胞未發(fā)現(xiàn)其他顯著的超微中國煤化工=[.AcmP結(jié)構(gòu)變化,但樹突內(nèi)變性體的存在至少提示這些[5]HCNMH神經(jīng)元的功能受到一定的損傷,只是損傷程度可能較transporters in alcoholism[J]. Am J Psychiatry, 1998, 155(11):1544輕而未累及到神經(jīng)元胞體。長期乙醇處理是否引起5HT能神經(jīng)元相似的病理改變及損傷機(jī)制尚有待于[6】 Heinz A,JmpWG, et al. 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Synapse, 2006, 59(5):270-276serotonin transporter genotype and in tito protein expression and alcohal[12]Li ShCh, Shi X, Shi GM, et a. Expression of serotonin transporter inneurotoxicity[ I]. Biol Psychiatry, 2000, 47(7): 643-649pregenual anterior cingulate cortex of alcoholics[J]. Clinical Focus(編舞鄒尚敏)《解剖學(xué)報(bào)》第十一屆編委會(huì)主編章靜波常務(wù)副主編周長滿主編徐群淵李云慶于恩華許增祿顧曉松羅建紅何大澄唐軍民高福祿編委D. Brynmor Thomas Elaine F, Reed Stephen W. Carmichael Leonard L. Seelig JR安威柏樹令蔡文琴常智杰陳東陳曉春陳耀星丁文龍竇犟華段相林方秀斌郭順根韓代書韓卉何欣黃東陽姜宗來金國華金連弘景雅鞠躬李和李繼承李金蓮林建銀劉斌劉佳劉樹偉盧光琇羅學(xué)港馬文麗穆祥牛建昭歐陽鉤饒志仁桑建利宿寶責(zé)蘇國輝唐茂林唐勇王海杰汪華僑王懷經(jīng)王亞平吳燕婉王云川席煥久謝富康徐存拴徐慧君羊惠君姚大衛(wèi)姚志彬應(yīng)大君原林曾園山張傳森張雷張志謙張欽憲張紹祥張世馥張衛(wèi)光張遠(yuǎn)強(qiáng)趙玲輝周國民朱長庚鄒仲之左伋左明雪(躺要以漢語拼音為序)中國煤化工CNMHG