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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (4): 38-44.doi: 10.6040/j.issn.1671-7554.0.2021.1381

• 临床医学 • 上一篇    

增服艾地苯醌对34例帕金森病抑郁患者的疗效观察

赵海龙1,2,王皓2,方雨晴2,毛飞2,赵张宁2,田祥奇2,徐新荣2,王敏3,李秀华2   

  • 发布日期:2022-04-22
  • 通讯作者: 李秀华. E-mail:lxh731023@126.com
  • 基金资助:
    山东省重大科技创新工程项目(2018CXGC1502);济南市临床医学科技创新计划(202019111)

Efficacy of additional idebenone in the treatment of 34 patients with Parkinsons disease with depression

ZHAO Hailong1,2, WANG Hao2, FANG Yuqing2, MAO Fei2, ZHAO Zhangning2, TIAN Xiangqi2, XU Xinrong2, WANG Min3, LI Xiuhua2   

  1. 1. Affiliated Hospital of Weifang Medical University, School of Clinical Medicine, Weifang Medical University, Weifang 261000, Shandong, China;
    2. Department of Neurology, The First Affiliated Hospital of Shandong Frist Medical University &
    Shandong Provincial Qianfoshan Hospital, Shandong Institute of Neuroimmunology, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan 250014, Shandong, China;
    3. Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan 250014, Shandong, China
  • Published:2022-04-22

摘要: 目的 观察艾地苯醌联合治疗帕金森病抑郁(PDD)患者的疗效,探讨艾地苯醌对PDD患者的神经保护机制。 方法 选择PDD患者68例,按随机数字表法分为对照组和观察组,每组34例。对照组接受多巴丝肼片和吡贝地尓缓释片治疗,多巴丝肼片初始剂量为0.125 g/次,3次/d,最高≤0.75 g/d,口服。吡贝地尔缓释片初始剂量50 mg/次,1次/d,最大剂量50 mg/次,3次/d,口服,连续治疗12周。观察组在对照组基础上加用艾地苯醌片,30 mg/次,3次/d,口服,连续治疗12周。监测两组患者汉密尔顿抑郁量表(HAMD)及其因子分、汉密尔顿焦虑量表(HAMA)及其因子分、统一帕金森评分量表-Ⅲ(UPDRS-Ⅲ)、帕金森病睡眠量表(PDSS)、简易精神状态检查量表(MMSE)、帕金森病生活质量问卷(PDQ-39)、外周血超氧化物歧化酶(SOD)变化情况。 结果 治疗后两组HAMD总分及各项因子均较治疗前降低,除体质量减轻和日夜变化外,观察组HAMD总分及焦虑/躯体化、认知障碍、阻滞、睡眠障碍和绝望感五项因子评分低于对照组(P<0.05);治疗后两组HAMA总分及精神性焦虑和躯体性焦虑两项因子分均较治疗前降低(P<0.05),且观察组低于对照组(P<0.05);治疗后两组UPDRS-Ⅲ评分较治疗前降低(P<0.05),且观察组低于对照组(P<0.05);治疗后两组PDSS评分均较治疗前增高(P<0.05),且观察组高于对照组(P<0.05);治疗后两组MMSE评分均较治疗前增高(P<0.05),且观察组高于对照组(P<0.05);治疗后两组PDQ-39评分均较治疗前降低(P<0.05),且观察组低于对照组(P<0.05);治疗12周后,观察组血SOD水平较治疗前增高,对照组血SOD水平较治疗前降低,两组SOD水平差异有统计学意义(P<0.05)。 结论 艾地苯醌联合治疗能够明显减轻PDD患者的抑郁症状,改善患者运动症状和部分非运动症状,增加PDD患者外周血SOD水平,提高生活质量。

关键词: 帕金森病, 抑郁, 艾地苯醌, 运动症状, 非运动症状

Abstract: Objective To observe the efficacy of idebenone in the treatment of Parkinsons disease with depression(PDD), and to explore its neuroprotective mechanism. Methods A total of 68 PDD patients were randomly divided into control group(n=34)and observation group(n=34). The control group received oral Dobasil tablets and Piribedil sustained-release tablets for 12 weeks. The initial dose of Dobasil tablets was 0.125 g/time, 3 times a day, and the highest dose was ≤0.75 g/d. The initial dose of Piribedil sustained-release tablets was 50 mg/time, once a day, and the maximum dose was 50 mg/time, 3 times a day. The observation group received oral idebenone plus the same treatment as the control group for 12 weeks. The dose was 30 mg/time, 3 times a day. The changes of Hamilton Depression Scale(HAMD)and its factor scores, Hamilton Anxiety Scale(HAMA)and its factor scores, Unified Parkinsons Scale-Ⅲ(UPDRS-Ⅲ), Parkinsons Disease Sleep Scale(PDSS), Mini Mental State Examination Scale(MMSE), 39-item Parkinsons Disease Questionnaire(PDQ-39)and superoxide dismutase(SOD)in the peripheral blood were monitored in the two groups. Results After treatment, the total score of HAMD and all factors in both groups were decreased. Except for weight loss and diurnal changes, the total score of HAMD and the scores of anxiety/somatization, cognitive impairment, block, sleep disorder and despair were significantly lower in the observation group than in the control group(P<0.05). The total score of HAMA and the scores of mental anxiety and somatic anxiety were decreased in both groups(P<0.05), and were significantly lower in the observation group than in the control group(P<0.05). The scores of UPDRS-Ⅲ were decreased in both groups(P<0.05), and were significantly lower in the observation group than in the control group(P<0.05). The PDSS scores were increased in both groups(P<0.05), and were significantly higher in the observation group than in the control group(P<0.05). The MMSE scores were increased in both groups(P<0.05), and were significantly higher in the observation group than in the control group(P<0.05). The PDQ-39 scores were decreased in both groups(P<0.05), and were significantly lower in the observation group than in the control group(P<0.05). The level of SOD was increased in the observation group but decreased in the control group, and the difference was statistically significant(P<0.05). Conclusion Additional idebenone can improve the depression, motor and some non-motor symptoms, increase the level of SOD in peripheral blood and improve the quality of life.

Key words: Parkinsons disease, Depression, Idebenone, Motor symptom, Non-motor symptom

中图分类号: 

  • R574
[1] Prell T, Witte OW, Grosskreutz J. Biomarkers for dementia, fatigue, and depression in Parkinson disease [J]. Front Neurol, 2019, 10: 195. doi:10.3389/fneur.2019.00195.
[2] Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review [J]. JAMA, 2020, 323(6): 548-560.
[3] Schrag A, Taddei RN. Depression and anxiety in Parkinsons disease [J]. Int Rev Neurobiol, 2017, 133: 623-655. doi: 10.1016/bs.irn.2017.05.024.
[4] Malpartida AB, Williamson M, Narendra DP, et al. Mitochondrial dysfunction and mitophagy in Parkinsons disease: from mechanism to therapy [J]. Trends Biochem Sci, 2021, 46(4): 329-343.
[5] Dorszewska J, Kowalska M, Prendecki M, et al. Oxidative stress factors in Parkinsons disease [J]. Neural Regen Res, 2021, 16(7): 1383-1391.
[6] Petschner P, Gonda X, Baksa D, et al. Genes linking mitochondrial function, cognitive impairment and depression are associated with endophenotypes serving precision medicine [J]. Neuroscience, 2018, 370: 207-217. doi:10.1016/j.neuroscience.2017.09.049.
[7] Bang Y, Lim J, Choi HJ. Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinsons disease: clues to early diagnosis and effective treatment [J]. Arch Pharmacal Res, 2021, 44(6): 588-604.
[8] Gueven N, Woolley K, Smith J. Border between natural product and drug: comparison of the related benzoquinones idebenone and coenzyme Q10 [J]. Redox Biol, 2015, 4: 289-295. doi:10.1016/j.redox.2015.01.009.
[9] Erb M, Hoffmann-Enger B, Deppe H, et al. Features of idebenone and related short-chain quinones that rescue ATP levels under conditions of impaired mitochondrial complex I [J]. PLoS One, 2012, 7(4): e36153.
[10] Surmeier DJ. Determinants of dopaminergic neuron loss in Parkinsons disease [J]. Febs J, 2018, 285(19): 3657-3668.
[11] Rocha EM, de Miranda B, Sanders LH. Alpha-synuclein: pathology, mitochondrial dysfunction and neuroinflammation in Parkinsons disease [J]. Neurobiol Dis, 2018, 109(Pt B): 249-257. doi: 10.1016/j.nbd.2017.04.004.
[12] Ludtmann MHR, Abramov AY. Mitochondrial calcium imbalance in Parkinsons disease [J]. Neurosci Lett, 2018, 663: 86-90. doi: 10.1016/j.neulet.2017.08.044.
[13] Grinberg LT, Rueb U, Alho ATDL, et al. Brainstem pathology and non-motor symptoms in PD [J]. J Neurol Sci, 2010, 289(1/2): 81-88.
[14] Park JS, Davis RL, Sue CM. Mitochondrial dysfunction in Parkinsons disease: new mechanistic insights and therapeutic perspectives [J]. Curr Neurol Neurosci Rep, 2018, 18(5): 21.
[15] Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinsons disease-an evidence-based medicine review [J]. Mov Disord, 2019, 34(2): 180-198.
[16] 陈海波, 陈生弟, 李淑华. 帕金森病抑郁、焦虑及精神病性障碍的诊断标准及治疗指南[J]. 中华神经科杂志, 2013, 46(1): 56-60.
[17] 张晓韬, 何天齐, 朱梅佳, 等. 艾地苯醌联合治疗帕金森病疗效的临床观察[J]. 山东大学学报(医学版), 2019, 57(4): 34-41. ZHANG Xiaotao, HE Tianqi, ZHU Meijia, et al. Clinical observation of the effects of idebenone on Parkinsons disease [J]. Journal of Shandong University(Health Sciences), 2019, 57(4): 34-41.
[18] Upneja A, Paul BS, Jain D, et al. Anxiety in Parkinsons disease: correlation with depression and quality of life [J]. J Neurosci Rural Pract, 2021, 12(2): 323-328.
[19] 刘瑜. 艾地苯醌联合常规药物治疗帕金森病疗效的临床观察[J]. 中国医药指南, 2020, 18(29): 97-98. LIU Yu. Clinical observation on the efficacy of idebenone combined with conventional drugs in the treatment of Parkinsons disease [J].Guide of China Medicine, 2020, 18(29): 97-98.
[20] Khatri DK, Choudhary M, Sood A, et al. Anxiety: an ignored aspect of Parkinsons disease lacking attention [J]. Biomed Pharmacother, 2020, 131: 110776. doi:10.1016/j.biopha.2020.110776.
[21] 马惠姿, 房进平, 冯涛, 等. 帕金森病患者不同程度抑郁在汉密尔顿抑郁量表的结构差异[J]. 中国康复理论与实践, 2021, 27(7): 829-833. MA Huizi, FANG Jinping, FENG Tao, et al. Structural differences of depression for patients with Parkinsons disease using Hamilton depression scale [J]. Chinese Journal of Rehabilitation Theory and Practice, 2021, 27(7): 829-833.
[22] 夏秋怡, 徐茂青, 霍青. 艾地苯醌结合美多芭对帕金森患者的疗效、步态及精神状态的影响[J]. 卒中与神经疾病, 2020, 27(5): 627-630. XIA Qiuyi, XU Maoqing, HUO Qing. The effects of idebenone combined with medoba on the curative effect, gait and mental state of patients with Parkinsons disease [J]. Stroke and Nervous Diseases, 2020, 27(5): 627-630.
[23] Jaber SM, Ge SX, Milstein JL, et al. Idebenone has distinct effects on mitochondrial respiration in cortical astrocytes compared to cortical neurons due to differential NQO1 activity [J]. J Neurosci, 2020, 40(23): 4609-4619.
[24] 杨硕, 赵丹鹏, 李琳, 等. 艾地苯醌对帕金森患者额叶磁共振波谱成像的影响[J]. 中国合理用药探索, 2019, 16(2): 124-126. YANG Shuo, ZHAO Danpeng, LI Lin, et al. Effect of idebenone on magnetic resonance spectroscopy imaging of frontal lobes in patients with Parkinsons disease [J]. Chinese Journal of Rational Drug Use, 2019, 16(2): 124-126.
[25] 徐珍. 艾地苯醌辅助治疗帕金森病疗效观察[J]. 临床合理用药杂志, 2020, 13(14): 35-37.
[26] Hanganu A, Degroot C, Monchi O, et al. Influence of depressive symptoms on dopaminergic treatment of Parkinsons disease[J]. Front Neurol, 2014, 5: 188. doi:10.3389/fneur.2014.00188.
[27] 黄骥, 阳军, 欧阳娟, 等.艾地苯醌联合多巴丝肼治疗帕金森病的临床研究[J].药物评价研究, 2020, 43(12):2501-2504. HUANG Ji, YANG Jun, OU Yangjuan, et al. Clinical study on idebenone combined levodopa and benserazide hydrochloride in treatment of Parkinsons disease [J]. Drug Evaluation Research, 2020, 43(12): 2501-2504.
[28] Avcı B, Günaydın C, Güvenç T, et al. Idebenone ameliorates rotenone-induced Parkinsons disease in rats through decreasing lipid peroxidation [J]. Neurochem Res, 2021, 46(3): 513-522.
[29] He Y, Tian YL, Han H, et al. The path linking disease severity and cognitive function with quality of life in Parkinsons disease: the mediating effect of activities of daily living and depression [J]. Heal Qual Life Outcomes, 2021, 19(1): 92.
[30] Lubomski M, Davis RL, Sue CM. Health-related quality of life for Parkinsons disease patients and their caregivers [J]. J Mov Disord, 2021, 14(1): 42-52.
[31] 康蓓, 慕生枝, 李妮妮, 等. 艾地苯醌联合多巴丝肼治疗帕金森病的疗效及对氧化应激因子的影响[J]. 山西医药杂志, 2019, 48(16): 1958-1960. KANG Bei, MU Shengzhi, LI Nini, et al. Efficacy observation of idebenone combined with levodopa and its effect on oxidative stress level in patients with Parkinsons disease [J]. Shanxi Medical Journal, 2019, 48(16): 1958-1960.
[32] Yan AJ, Liu ZH, Song L, et al. Idebenone alleviates neuroinflammation and modulates microglial polarization in LPS-Stimulated bv2 cells and MPTP-Induced Parkinsons disease mice [J]. Front Cell Neurosci, 2018, 12: 529. doi: 10.3389/fncel. 2018.00529.
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