吡贝地尔对帕金森病模型大鼠脑多巴胺D2受体的影响

目的研究常用抗帕金森药多巴胺受体激动剂吡贝地尔对脑多巴胺D2受体的影响。方法立体定位右侧纹状体注射6-羟多巴胺制备偏侧帕金森病大鼠模型,模型成功后予吡贝地尔灌胃治疗[30mg/(kg·d)]5周。分4组(正常组、术后4周帕金森病模型大鼠组、术后9周帕金森病模型大鼠经吡贝地尔治疗组、术后9周帕金森病模型大鼠未治疗组)行125I-依匹必利(125I-epidepride)大鼠脑多巴胺D2受体放射自显影。图像分析得到纹状体与小脑的平均光密度值,计算并比较各组左、右两侧脑多巴胺D2受体的特异性放射性摄取比值(纹状体/小脑-1)的变化。结果正常大鼠脑多巴胺D2受体对依匹必利的特异性放射性摄取比值左、右两侧差异无统计学意义;成为帕金森病模型后,右侧(损毁侧)比值较正常稍升高,但差异无统计学意义;未治疗组帕金森病模型大鼠双侧比值较刚成模型时均明显降低,右侧(损毁侧)比值仍较左侧高;经吡贝地尔治疗后,双侧比值较未治疗组进一步降低,右侧(损毁侧)降低甚,比值较左侧低。结论长期吡贝地尔治疗可能会使帕金森病模型大鼠双侧脑多巴胺D2受体的数量减少,损毁侧减少为甚。     

吡贝地尔对早期帕金森病非运动症状的影响

目的:观察复方左旋多巴和吡贝地尔单用和联合应用对早期帕金森病(PD)患者非运动症状的影响。方法:早期PD患者67例,分为单用吡贝地尔组(25例),复方左旋多巴与吡贝地尔联合用药组(20例),单用复方左旋多巴组(22例)。采用UPDRS-Ⅰ、Ⅱ,PD生活质量评定量表,Hamilton抑郁量表和PD睡眠评分量表对患者进行基线评定,并在治疗后1、3和6个月进行跟踪随访。结果:联合用药组UPDRS-Ⅰ、Ⅱ、抑郁情绪评分、睡眠质量评分以及生活质量评分在各个随访点均较用药前有显著改善;吡贝地尔组Hamilton抑郁评分在各观察窗内均较用药前降低;复方左旋多巴组在第6个月出现睡眠状况的恶化。结论:吡贝地尔单用或联合复方旋多巴应用,吡贝地尔可以较好地改善早期PD患者的精神、情绪和睡眠等非运动症状;早期联合应用吡贝地尔可显著提高患者生活质量。     

左旋多巴对帕金森病大鼠脑多巴胺神经元影响的放射自显影研究

摘要 目的 了解左旋多巴治疗对帕金森病大鼠模型脑内多巴胺神经元的影响。方法 建立右侧毁损帕金森病大鼠模型,左旋多巴治疗(20mg/kg/d) 1月,并设生理盐水干预组。停药2天后,尾静脉注射99mTc-TRODAT-1 0.2ml(800μGi),2h后先采集鼠脑部DAT显像图像再处死,测定放射性计数,计算左右脑每克放射性计数值及左右之比R值。结果①假手术组大鼠多巴胺转运体对99mTc-TRODAT-1特异性放射性摄取左右两侧差异无显著性(p>0.05),图像清晰,对称分布于基底节区;②帕金森病模型组鼠的左右两侧差异有显著性(p<0.01),R值显著升高(1.419±0.187, p<0.01),损伤侧(右侧脑)放射性摄取明显减少,图像中右侧基底节区明显稀疏;③旋多巴治疗组,部分鼠损伤侧(右侧脑)放射性摄取进一步减少,R值较帕金森病模型鼠组进一步升高(1.649±0.353, p<0.05),图像中右侧基底节区更加稀疏,临床观察评分有异动症并发（60%）;而未发生异动症的大鼠其R比值则下降(1.202±0.194),右侧放射性摄取回升,图像也支持。结论 左旋多巴治疗后部分帕金森病鼠脑内多巴胺转运体的数目及功能进一步下调,对多巴胺能神经元有毒性作用,易促发异动症。但合适剂量的左旋多巴也可促进损伤的多巴胺能神经元功能恢复。 关键词 帕金森病 左旋多巴 多巴胺转运体 99mTc-TRODAT-1     

吡贝地尔治疗帕金森病运动波动的疗效观察

目的　观察吡贝地尔（ 泰舒达） 治疗帕金森病运动波动的临床疗效。方法　以５０ 例帕金森病运动波动患者治疗前后为自身对照的研究方法,在原治疗基础上每日加用吡贝地尔１００ ～１５０ ｍｇ ,连续观察８ 周。临床疗效按帕金森病改良 Ｗｅｂｓｔｅｒ １０ 大症状评分法为观察指标。结果　吡贝地尔对运动波动的剂末现象、开关现象和痛性痉挛的有效比例分别为１９／２４ 、９／２２ 和３／４ ,总有效率为６２ ％ 。不良反应以恶心呕吐多见。结论　吡贝地尔治疗帕金森病运动波动疗效肯定,口服吗叮啉可使不良反应减轻或缓解。     

帕金森病脑内多巴胺转运体的SPECT显像研究

多巴胺转运体是再摄取突触间隙多巴胺的功能蛋白。早期帕金森病患者的多巴胺转运体水平明显降低。对多巴胺转运体的深入研究将有助于帕金森病病因、发病机制的阐明和早期诊断。用放射性同位素标记的多巴胺转运体配体可用于它的ＳＰＥＣＴ显像。本文就常用多巴胺转运体配体恃点,ＳＰＥＣＦ显像研究方法及其意义作一综述。     

吡贝地尔致睡眠发作一例

1 病例报告 患者女,57岁,主因"突发睡意7个月"于2006-02就诊于作者医院神经内科门诊.     

多巴胺转运体显像对特发性震颤与早期帕金森病的鉴别诊断价值

目的探讨多巴胺转运体(DAT)显像对特发性震颤(ET)、早期帕金森病(PD)鉴别诊断的价值.方法以99mTc-2β-[N,N'-双(2-巯乙基)乙撑二胺基]甲基-3β-(4-氯苯基)托烷(99mTc-TRODAT-1)为显像剂,用单光子发射计算机断层扫描(SPECT)对8例姿势性震颤(PT)患者,5例姿势性震颤伴静止性震颤(PT+RT)患者、12例早期PD(H-Y I级)患者进行DAT显像.结果与PT组相比,PT+RT组两侧纹状体(ST)与枕叶(OC)的ST/OC均值略高,但无显著性差异;早期PD组ST/OC均值显著性降低.PT+RT组两侧ST/OC均值明显高于早期PD组患肢对侧,但与其同侧无显著性差异.结论PT伴RT的ET患者存在轻度多巴胺神经元的缺失,99mTc-TRODAT-1 SPECT DAT显像对ET和早期PD有鉴别诊断的价值.     

吡贝地尔治疗帕金森病晚期运动并发症的临床研究

帕金森病(PD)是一种慢性进行性神经系统变性疾病,多发生于中老年人,是由于脑内黑质多巴胺能神经元丢失引起的多巴胺缺乏所致[1].目前主要是应用左旋多巴结合多巴脱羧酶抑制剂等对症治疗.初期疗效显著,但长期治疗疗效减退,还会导致症状波动、异动症等运动并发症及精神障碍等非运动症状,严重影响患者的生活质量,治疗非常棘手.吡贝地尔是一种非麦角类缓释型多巴胺受体激动剂,可以直接作用于纹状体多巴胺受体,缓解PD的症状.过去在PD初期使用吡贝地尔治疗的研究较多,但对于治疗晚期并发症的研究较少,本研究旨在系统评价吡贝地尔在治疗PD晚期运动并发症的疗效及安全性,为晚期PD患者临床优化治疗提供依据.     

C57BL小鼠帕金森病模型多巴胺转运蛋白99mTc-TRODAT-1放射自显影研究

Objective　To evaluate the density change of dopamine transporter(DAT)in striatum of C57BL mouse model of Parkinsonism.Methods　In this study,MPTP and Tc-TRODAT-1 were injected intravenously to mice respectly in several groups.Autoradiography and histoimmunochemical stain technology were used respectly.Result　At 1h postinjection of ^99m　Tc-TRODAT-1,exvivo autoradiography indicated that the striatum displayed the intense radioactivity in the control group.In group of MPTP lesion for 1 day,the radioactivity of the striatum was reduced compared with that of control group.In groups of 3,5 and 7 days,the radioactivity of the striatum was decreased,and the degree of decrement was related positive to the days of MPTP lesion,and in group of 7 days,the radioactivity in striatium almost disappeared.The loss of TH positive cells and fibres in substantia nigra and striatum of models were found,and the degree of loss was also related positive to the days with MPTP lesion.Conclusion　The progressive degeneration of Parkinson^,s disease was mimicked by C57BL mouse model of parkinsonism with the different degree of MPTP lesioned substantia nigra.^99mTc-TRODAT-1 as a imaging ligand for DAT may be useful for the early diagnosis of PD.     

盐酸苯海索联合吡贝地尔治疗帕金森病的效果及安全性分析

目的观察盐酸苯海索联合吡贝地尔治疗帕金森病的临床疗效及安全性。方法选取2013-01—2015-06我科收治的诊断为帕金森病患者80例,按随机数字表法分为观察组及对照组各40例,对照组给予吡贝地尔常规治疗,观察组在对照组基础上加用盐酸苯海索治疗,记录并分析治疗1个月后2组患者UPDRS得分、Webster得分及SCL-90因子分值情况。结果治疗4周后观察组UPDRS评分为6.95±1.34,低于对照组的12.73±1.58,Webster得分11.51±3.04,低于对照组的16.24±2.79,躯体、抑郁、焦虑、人际关系SCL-90因子分值分别为(1.68±0.13、1.32±0.42、1.43±0.17、1.31±0.48)分,均优于对照组(1.91±0.24、1.92±0.46、1.69±0.15、1.85±0.52),差异均有统计学意义(P0.05)。2组均未见明显不良反应。结论盐酸苯海索联合吡贝地尔治疗帕金森病疗效肯定、确切,与单独使用吡贝地尔常规治疗相比无明显不良反应,能显著提高怕帕金森病患者生命生活质量,值得临床应用。     

C57BL小鼠帕金森病模型多巴胺转运蛋白99mTc-TRODAT-1放射自显影研究

目的　评价不同损毁程度 Ｃ５７ Ｂ Ｌ 小鼠帕金森病（ Ｐ Ｄ）模型纹状体多巴胺转运蛋白（ Ｄ Ａ Ｔ）的变化。方法　根据腹腔注射 Ｍ Ｐ Ｔ Ｐ 的天数将小鼠分为 １、３、５ 和 ７ｄ 模型组以及对照组,静脉注射９９ｍ Ｔｃ Ｔ Ｒ Ｏ Ｄ Ａ Ｔ１６ｍ Ｃｉ,１ｈ 后处死行脑纹状体放射自显影,同时行免疫组化酪氨酸羟化酶（ Ｔ Ｈ）染色。结果　对照组的放射自显影可见９９ｍ Ｔｃ Ｔ Ｒ Ｏ Ｄ Ａ Ｔ１ 于纹状体部位有高度放射性聚集,且两侧纹状体基本相同。注射 Ｍ Ｐ Ｔ Ｐ １ｄ 者,其纹状体的放射性浓集比对照组有所下降。注射 Ｍ Ｐ Ｔ Ｐ ３、５ 及 ７ｄ 者,两侧纹状体的放射性浓集逐日降低,第 ７ｄ 者几乎消失。 Ｔ Ｈ 染色发现黑质 Ｔ Ｈ 阳性神经元亦随注射 Ｍ Ｐ Ｔ Ｐ 天数的增加而数量减少。结论　不同程度损毁的 Ｃ５７ Ｂ Ｌ 小鼠 Ｐ Ｄ 模型可模拟 Ｐ Ｄ 的发展过程,９９ｍ Ｔｃ Ｔ Ｒ Ｏ Ｄ Ａ Ｔ１ 作为 Ｄ Ａ Ｔ 的显影剂可用于早期诊断的神经显像学研究。     

Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study

Objectives

To evaluate patients with “clinically established” psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism.

Patients and methods

Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n = 5) and healthy control subjects (n = 5).

Results

The mean age (years-old) at first evaluation in the PsyP group was 37.4 ± 3.7, and the mean disease duration (years) was 3.9 ± 1.2. DAT BPs (means ± standard deviations) on right/left caudate were, respectively, 0.69 ± 0.18 and 0.70 ± 0.18 in the PD group versus 1.17 ± 0.06 and 1.12 ± 0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48 ± 0.10 and 0.45 ± 0.06 in the PD group versus 1.10 ± 0.10 and 1.21 ± 0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (≤0.70) for controls, implying pre-synaptic dopaminergic deficit.

Conclusions

Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.     

多巴胺转运体SPECT显像评估帕金森病严重程度的研究

目的本研究探讨显像评估帕金森病严重程度的意义.方法对15例对照者和30例帕金森病患者(根据Hoehn-Yahr分级分为早期组18例,中晚期组12例)行99mTc-TRODAT-1 DAT SPECT断层显像,注射示踪剂2～3 h后采集图像,勾画出感兴趣区(双侧纹状体和枕叶),计算机自动计算感兴趣区的放射性计数,最后测算出纹状体与枕叶部位的放射性计数比值和非对称性指数,并进行比较分析.结果对照组特异性放射性计数比值是0.58±0.16(左侧)、0.56±0.32(右侧),早期帕金森病组特异性放射性计数比值为0.40±0.33(症状对侧或症状严重肢体对侧)、0.51±0.12(症状同侧),中晚期帕金森病组特异性放射性计数比值为0.23±0.18(症状严重肢体对侧)、0.40±0.17(症状同侧);对照组非对称性指数是5.12±0.48,早期帕金森病组为9.05±14.61,中晚期组为20.67±14.2,3组间比较均有显著性差异(P＜0.05).结论多巴胺转运体99mTc-TRODAT-1 SPECT显像有助于帕金森病严重程度的判断.     

百草枯干预不同时间后DAT和VMAT2基因表达的时程变化

目的 探讨百草枯干预后黑质部纹状体通路DAT和VMAT2基因表达的时程变化。方法 用口服百草枯的途径，建立小鼠帕金森病模型；应用RT-PCR技术观察小鼠口服百草枯（每日10mg/kg）不同时间后黑质部DAT和VMAT2基因表达的变化。结果 从口服百草枯2周起，小鼠黑质部DAT和VMAT2的基因表达开始减少，并且随着喂食时间的延长逐渐减少。结论 在百草枯致PD的早期，DAT和VMAT2的基因表达就受到损害，并且随着百草枯所致PD病程的延续，受损的程度逐渐加重，表明DAT和VMAT2均可能参与了百草枯致帕金森病的发病机制。     

帕金森病大鼠模型的实验研究

目的 观察帕金森病（PD）大鼠模型行为学变化特点。方法 通过改良PD大鼠模型,观察30只大鼠模型成功后1、7、14天旋转行为的多项指标变化,如：启动时间、持续时间、最高转速、旋转圈数等。结果 1－14天时PD大鼠启动时间逐渐延长、持续时间逐渐缩短,最高转速与旋转圈数不变。结论 改良PD大鼠模型制作方法科学、简单、定位可靠;PD大鼠最高旋转速度、旋转圈数能反映黑质损伤程度。     

Activity and acceptability of piribedil in Parkinson's disease: a multicentre study

Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.1, SD 0.6 (43–79) years with a 2.1, SD 0.2 (1–15) year history of Parkinson's disease. Mean disease stage was 1.82 (1–4) by the Hoehn and Yahr classification. Tremor was the predominant clinical feature in 42 patients; the remaining 71 patients displayed the full parkinsonian syndrom. Trivastal 50 mg LP was prescribed stepwise up to doses of 150–250 (207, SD 6.4) mg/day at the end of 3 months. No concomitant antiparkinsonian medication was given. Patients were clinically assessed at 1, 2 and 3 months on the Webster scale, a specific tremor scale and the HARD depression scale. Mean results were as follows in the 90 patients completing the study. On the Webster scale, tremor fell from 1.7 to 1 (–41%,P<0.001), bradykinesia=" from=" 1.5=" to=" 0.8=">P<0.001) and=" rigidity=" from=" 1.3=" to=" 0.9=">P < 0.001);=" on=" the=" specific=" scale,=" rest=" tremor=" decreased=" in=" daily=" duration=" and=" amplitude=" from=" 3.9=" to=" 2.4=">P < 0.001)=" and=" from=" 2.9=" to=" 2.1=">P < 0.001),=" respectively.=" the=" 32=" patients=" in=" whom=" tremor=" was=" the=" predominant=" feature=" improved=" their=" total=" score=" on=" the=" webster=" scale=" from=" 5.8=" to=" 4.7=">P<0.05) and=" their=" tremor=" score=" from=" 1.7=" to=" 1.2=">P < 0.05).=" the=" 58=" patients=" with=" the=" full=" parkinsonian=" syndrom=" improved=" their=" total=" webster=" score=" from=" 11.8=" to=" 6.9=">P < 0.001).=" eight=" of=" the=" ten=" items=" on=" the=" scale=" were=" significantly=" reduced,=" from=" between=" 33%=" (facial=" expression)=" to=" 53%=" (manual=" bradykinesia).=" the=" depression=" rating=" fell=" from=" 10.2=" to=" 7.3=">P < 0.001),=" the=" most=" marked=" improvement=" being=" in=" mood=" and=" inhibition.=" in=" conclusion,=" monotherapy=" with=" trivastal=" 50=" mg=" lp=" at=" a=" mean=" dose=" of=" 200=" mg/day=" is=" effective=" within=" 1=" month=" regarding=" the=" major=" features=" of=" parkinson's=">     

Differential effects of scopolamine on in vivo binding of dopamine transporter and vesicular monoamine transporter radioligands in rat brain

The in vivo equilibrium specific binding of d-threo-[3H]methylphenidate, a radioligand for the dopamine transporter (DAT), and +-alpha-[3H]dihydrotetrabenazine, a radioligand for the vesicular monoamine transporter (VMAT2), were examined in rat brain with and without prior administration of 5 mg/kg scopolamine. Drug-treated animals exhibited a 30% increase in d-threo-[3H]methylphenidate binding to the DAT in the striatum relative to controls. No changes in specific binding of +-alpha-[3H]dihydrotetrabenazine were observed in any brain region following scopolamine pretreatment. Cholinergic drugs thus differentially affect in vivo specific binding of DAT and VMAT2 radioligands, suggesting this should be a consideration in selection of in vivo markers for imaging studies of dopaminergic terminals in the brain of animals and humans.     

Lower dopamine transporter density in an asymptomatic patient with Kleine-Levin syndrome

Background –  Kleine–Levin syndrome (KLS) is a rare disorder whose pathophysiological mechanisms remain unknown.
Patients and methods –  To investigate dopamine abnormalities in KLS, a [^99mTc] – TRODAT-1 single photon emission computerized tomography (SPECT) was performed in a patient with KLS during the asymptomatic period and compared with three matched healthy controls.
Results –  The patient had 14% lower striatal dopamine transporter binding potential (DAT-BP) compared to the mean DAT-BP of three healthy controls.
Conclusion –  This study provides in vivo evidence for abnormalities in the DAT-BP, suggesting an involvement of the dopaminergic system in the pathophysiology of KLS.