司来吉兰对早期帕金森病患者多巴胺能神经元的影响

背景司来吉兰可有效缓解早期帕金森病的运动障碍症状,但对于早期帕金森病预后的影响争议甚多.神经影像学的研究进展使得帕金森病多巴胺能神经元的变性程度客观标记成为可能.目的利用影像学观察研究司来吉兰对早期帕金森病多巴胺能神经元的影响.设计以患者为研究对象的随机对照实验.单位一所军队医院的神经内科和一所军医大学医院的核医学科、神经内科.对象2001-04/10第二军医大学长海医院神经内科帕金森病专病门诊筛选的25例未经任何药物治疗的早期帕金森病患者.干预25例患者随机分为安慰剂组和司来吉兰治疗组,安慰剂组13例,司来吉兰治疗组12例.联合帕金森病量表(Unified Parkinson's disease rating scale,PDRS)评分后,按照逐渐增量的原则,分别给予安慰剂和司来吉兰治疗(起始剂量均为0.05 mg).每周增加0.05 mg,经过4周的加量期,剂量均达到0.2 mg,此后维持剂量恒定.于入组时、治疗13个月后分别行多巴胺转运蛋白(99Tcm-TRODAT-1)单光子发射型计算机体层扫描(single photon emission-computeredtomography,PECT)检查,半定量法分析起病肢体对侧、同侧纹状体放射计数.于入组时、治疗6个月、治疗13个月后分别进行UPDRS评分.主要观察指标①主要结局两组治疗13个月后起病肢体对侧、同侧纹状体99Tcm-TRODAT-1特异性摄取降低百分率的比较.②次要结局两组UPDRS评分的变化.结果治疗13个月后起病肢体对侧、同侧纹状体99Tcm-TRODAT-1特异性摄取降低百分率分别为安慰剂组(28.9±13.0)%、(31.8±15.6)%;司来吉兰治疗组(30.39±14.7)%、(32.6±16.6)%,两组之间比较差异无显著性意义(P＞0.05).UPDRS评分治疗6个月后,安慰剂组(23.7±4.3)分,司来吉兰治疗组(13.1±5.5)分;治疗13个月后,安慰剂组(27.0±4.3)分,司来吉兰治疗组(9.8±4.8)分,司来吉兰治疗组明显优于安慰剂组(P＜0.05).结论司来吉兰对早期帕金森病的临床效果较好,而且不加重纹状体多巴胺能神经元的凋亡.

Influence of selegiline on dopaminergic neurons in patients with early Parkinson disease

BACKGROUND: Selegiline can effectively alleviate motor disorder symptoms during the earlier stage of Parkinson disease(PD),but the influence on prognosis is still warmly discussed. With the development of neuroiconologicai study,the objective predictor for dopaminergic neuronal degeneration in PD would became possible.OBJECTIVE: To observe the influence of selegiline on dopaminergic neurons in earlier stage of PD with the aid of iconology.DESIGN: Randomized controlled study based on patients.SETTING: Neurological department in a military hospital of Chinese PLA,the nuclear medicine and neurological department in a military medical hospital of Chinese PLA.PARTICIPANTS: Between April and December 2001,25 patients were selected from PD specific clinic of Changhai Hospital,the Second Military Medical University of Chinese PLA. They were confirmed of earlier stage of PD without given any related drugs.INTERVENTIONS: Totally 25 patients were randomly divided into placebo group of 13 cases and selegiline group of 12 cases. After assessed with unified PD rating scale(UPDRS),they were given placebo and selegiline respectively with the dosage gradually increased from 0.05 mg at the beginning and added with 0.05 mg every week for four weeks until reaching the sustaining dosage of 0.2 mg. Dopamine transporting protein (99Tcm-TRODAT-1) examination and single photon emission-computerized tomography (SPECT) were performed at entering the experiment and after the treatment for 13 months,and semi-quantitative analysis was used for counting striatal emission of the ipsilateral and contralateral side. Scores for UPDRS were obtained at entering the experiment,after the treatment for 6months and 13 months.MAIN OUTCOME MEASURES:①Main outcomes:The differences ofstriatal 99Tcm-TRODAT-1 specific intake decreasing percentage on ipsilateral and contralateral side were compared between the two groups after the treatment for 13 months.②Subordinate outcome:Scores for UPDRS of the two groups was also compared.RESULTS: After the treatment for 13 months,striatal 99Tcm-TRODAT-1 specific intake decreasing percentages were (28.9 ± 13.0)% and(31.8 ± 15.6) % on ipsilateral and contralateral side of placebo group compared with the corresponding (30.39 ± 14. 7)% and(32.6 ± 16. 6)% of the selegiline group,the difference was of no statistical significance( P ＞ 0.05). Scores for UPDR was(23.7 ±4.3) in placebo group and(13.1 ± 5.5) in selegiline group after the treatment for 6 months,and(27.0 ±4.3) and(9. 8 ±4. 8) after the treatment for 13 months,indicating that slegiline group was obviously better than placebo group( P ＜ 0. 05).CONCLUSION: Selegiline showed better therapeutic effect in the treatment of earlier-stage PD without increasing the apoptosis of striatal dopaminergic neurons.