艾地苯醌联合治疗帕金森病疗效的临床观察
|
摘要
目的观察艾地苯醌(IDE)对帕金森病患者的运动及非运动症状的改善情况,探讨IDE对帕金森病患者的神经保护作用。方法选取帕金森病患者200例随机分为IDE治疗组(常规治疗+IDE治疗)和常规治疗组(常规治疗),分别监测两组治疗前及治疗后3、6、9、12、15、18个月统一帕金森评分量表(UPDRS)-Ⅲ(开期、关期)、蒙特利尔认知评估量表(MOCA)、匹兹堡睡眠质量指数量表(PSQI)、帕金森非运动症状评价量表(NMSS)评分变化,监测治疗前及治疗后6、12、18个月血超氧化物歧化酶、血尿酸结果的变化。结果①IDE治疗组治疗后3、6、9、12、15、18个月UPDRS-Ⅲ(开期)评分分别为16.64±6.08、14.69±5.33、12.81±4.73、11.04±3.95、9.66±3.43、8.47±3.09,常规治疗组治疗后3、6、9、12、15、18个月UPDRS-Ⅲ(开期)评分分别为16.79±6.44、15.64±6.16、14.58±5.86、13.54±5.56、12.41±5.11、11.16±4.65;治疗后9、12、15、18个月UPDRS-Ⅲ(开期)评分同一时间点相比较,IDE治疗组低于常规治疗组,且差异有统计学意义(P<0.05);治疗后3、6个月两组UPDRS-Ⅲ(开期)评分相比较,差异无统计学意义(P>0.05)。②IDE治疗组治疗后3、6、9、12、15、18个月UPDRS-Ⅲ(关期)评分分别为23.09±8.63、21.10±7.13、19.30±6.24、17.39±5.37、15.65±4.78、14.05±4.25;常规治疗组治疗后3、6、9、12、15、18个月UPDRS-Ⅲ(关期)评分分别为19.85±7.20、19.63±6.85、19.13±6.57、18.32±6.28、17.35±5.97、16.10±5.64;两组治疗后15、18个月UPDRS-Ⅲ(关期)评分同一时间点比较,IDE治疗组低于常规治疗组,且差异有统计学意义(P<0.05);两组治疗后3、6、9、12个月UPDRS-Ⅲ(关期)评分同一时间相比较,差异无统计学意义(P>0.05)。③IDE治疗组在治疗后3、6、9、12、15、18个月MOCA评分分别为21.68±4.59、23.02±3.60、24.39±2.66、25.30±2.12、25.94±1.81、24.72±2.23;常规治疗组在治疗后3、6、9、12、15、18个月MOCA评分分别为22.13±4.64、22.69±4.23、23.40±3.69、24.20±3.18、25.17±2.66、24.27±2.94;治疗后9、12、15个月MOCA评分同一时间点相比较,IDE治疗组高于常规治疗组,且差异有统计学意义(P<0.05);两组治疗后3、6、18个月MOCA评分同一时间点相比较,差异无统计学意义(P>0.05)。④IDE治疗组在治疗后3、6、9、12、15、18个月PSQI评分别为6.36±4.26、5.33±3.84、4.59±3.45、3.32±2.92、2.71±2.38、2.20±2.02,常规治疗组在治疗后3、6、9、12、15、18个月PSQI评分为6.12±4.19、5.25±3.85、4.50±3.50、3.51±3.27、3.26±3.03、3.04±2.84,两组治疗后18个月PSQI评分同一时间点相比较,IDE治疗组优于常规治疗组,且差异有统计学意义(P<0.05);两组治疗后3、6、9、12、15个月PSQI评分同一时间点比较,差异无统计学意义(P>0.05)。⑤IDE治疗组在治疗后3、6、9、12、15、18个月NMSS评分分别为54.69±31.87、52.01±30.11、46.84±30.76、41.20±29.60、38.77±26.67、36.63±25.39;常规治疗组在治疗后3、6、9、12、15、18个月NMSS评分为54.56±33.26、52.42±32.02、50.38±30.65、46.97±28.05、43.18±24.65、41.03±23.48;两组在治疗后3、6、9、12、15、18个月NMSS评分同一时间相比较,差异无统计学意义(P>0.05)。⑥IDE治疗组在治疗后6、12、18个月血尿酸水平分别为(253.81±111.86)μmol/L、(272.56±111.04)μmol/L、(280.12±111.09)μmol/L,常规治疗组在治疗后6、12、18个月血尿酸水平分别为(217.82±103.24)μmol/L、(198.90±102.36)μmol/L、(191.97±101.81)μmol/L,两组治疗后6、12、18个月血尿酸水平同一时间点相比较,IDE治疗组优于常规治疗组,差异有统计学意义(P<0.05)。⑦IDE治疗组在治疗后6、12、18个月血超氧化物歧化酶水平分别为(154.45±39.96)U/mL、(162.45±42.08)U/mL、(172.90±41.78)U/mL,常规治疗组在治疗后6、12、18个月血超氧化物歧化酶水平分别为(126.47±41.30)U/mL、(119.36±39.71)U/mL、(112.17±37.17)U/mL,两组治疗后6、12、18个月血超氧化物歧化酶水平同一时间点相比较,IDE治疗组优于常规治疗组,差异有统计学意义(P<0.05)。结论 IDE能改善帕金森病患者的运动及部分非运动症状,延缓病情的进展,对帕金森病具有一定的神经保护作用。
Objective To investigate the effects of idebenone(IDE) on the motor and non-motor symptoms in patients with Parkinson's disease(PD) and to explore its neuroprotective effect. Methods A total of 200 PD patients were randomly divided into the IDE group(IDE+routine treatment) and routine group(routine treatment). The scores of Unified Parkinson's Disease Rating-III(on-stimulation), UPDRS-III(off-stimulation), Montreal Cognitive Assessment(MOCA), Pittsburgh Sleep Quality Index(PSQI), and Non-Motor Symptoms Scale for Parkinson's Disease(NMSS) were monitored before treatment and 3, 6, 9, 12, 15 and 18 months after treatment. Furthermore, changes of plasma superoxide dismutase(SOD) and uric acid were detected before treatment and 6, 12 and 18 months after treatment. Results ① In month 3, 6, 9, 12, 15 and 18 after treatment, the score of UPDRS-III(on-stimulation) in the IDE group versus that in the routine group was 16.64±6.08 vs 16.79±6.44, 14.69±5.33 vs 15.64±6.16, 12.81±4.73 vs 14.58±5.86, 11.04±3.95 vs 13.54±5.56, 9.664±3.43 vs 12.41±5.11 and 8.471±3.09 vs 11.16±4.65, respectively. In month 3 and 6, there was no difference between the two groups(P>0.05). In month 9, 12, 15 and 18, the score was significantly lower in the IDE group than in the routine group(P<0.05). ② In month 3, 6, 9, 12, 15 and 18 after treatment, the score of UPDRS-III(off-stimulation) in the IDE group versus that in the routine group was 23.09±8.63 vs 19.85±7.20, 21.10±7.13 vs 19.63±6.85, 19.30±6.24 vs 19.13±6.57, 17.39±5.37 vs 18.32±6.28, 15.65±4.78 vs 17.35±5.97 and 14.05±4.25 vs 16.10±5.64, respectively. In month 3, 6, 9 and 12, there was no difference between the two groups(P>0.05). In month 15 and 18, the score was significantly lower in the IDE group than in the routine group(P<0.05). ③ In month 3, 6, 9, 12, 15 and 18 after treatment, the MOCA score in the IDE group versus that in the routine group was 21.68±4.59 vs 22.13±4.64, 23.02±3.60 vs 22.69±4.23, 24.39±2.66 vs 23.40±3.69, 25.30±2.12 vs 24.20±3.18, 25.94±1.81 vs 25.17±2.66 and 24.72±2.23 vs 24.27±2.94, respectively. In month 3, 6 and 18, there was no significant difference between the two groups(P>0.05). In month 9, 12 and 15, the score was significantly higher in the IDE group than in the routine group(P<0.05). ④ In month 3, 6, 9, 12, 15 and 18 after treatment, the PSQI score in the IDE group versus that in the routine group was 6.36±4.26 vs 6.12±4.19, 5.33±3.84 vs 5.25±3.85, 4.59±3.45 vs 4.50±3.50, 3.32±2.92 vs 3.51±3.27, 2.71±2.38 vs 3.26±3.03 and 2.20±2.02 vs 3.04±2.84, respectively. In month 3, 6, 9, 12 and 15, there was no difference between the two groups(P>0.05). In month 18, the score was significantly lower in the IDE group than in the routine group(P<0.05). ⑤ In month 3, 6, 9, 12, 15 and 18 after treatment, the NMSS score in the IDE group versus that in the routine group was 54.6±31.87 vs 54.56±33.26, 52.01±30.11 vs 52.42±32.02, 46.84±30.76 vs 50.38±30.65, 41.20±29.60 vs 46.97±28.05, 38.77±26.67 vs 43.18±24.65, 36.63±25.39 vs 41.03±23.48, respectively. There was no significant difference between the two groups(P>0.05). ⑥ In month 6, 12 and 18 after treatment, the level of uric acid in the IDE group versus the routine group was(253.81±111.86) vs(217.82±103.24) μmol/L,(272.56±111.04) vs(198.90±102.36) μmol/L, and(280.12±111.09) μmol/L vs(191.97±101.81) μmol/L, respectively. The level of uric acid was significantly higher in the IDE group than in the routine group(P<0.05). ⑦ In month 6, 12 and 18, the SOD level in the IDE group versus that in the routine group was(154.45±39.96) vs(126.47±41.30) U/mL,(162.45±42.08) vs(119.36±39.71) U/mL, and(172.90±41.78) vs(112.17±37.17) U/mL, respectively. The SOD level was significantly higher in the IDE group than in the routine group(P<0.05). Conclusion IDE can improve the motor and non-motor symptoms in PD patients and slow down the progression of the disease. It has a certain neuroprotective effect on PD.
Objective To investigate the effects of idebenone(IDE) on the motor and non-motor symptoms in patients with Parkinson's disease(PD) and to explore its neuroprotective effect. Methods A total of 200 PD patients were randomly divided into the IDE group(IDE+routine treatment) and routine group(routine treatment). The scores of Unified Parkinson's Disease Rating-III(on-stimulation), UPDRS-III(off-stimulation), Montreal Cognitive Assessment(MOCA), Pittsburgh Sleep Quality Index(PSQI), and Non-Motor Symptoms Scale for Parkinson's Disease(NMSS) were monitored before treatment and 3, 6, 9, 12, 15 and 18 months after treatment. Furthermore, changes of plasma superoxide dismutase(SOD) and uric acid were detected before treatment and 6, 12 and 18 months after treatment. Results ① In month 3, 6, 9, 12, 15 and 18 after treatment, the score of UPDRS-III(on-stimulation) in the IDE group versus that in the routine group was 16.64±6.08 vs 16.79±6.44, 14.69±5.33 vs 15.64±6.16, 12.81±4.73 vs 14.58±5.86, 11.04±3.95 vs 13.54±5.56, 9.664±3.43 vs 12.41±5.11 and 8.471±3.09 vs 11.16±4.65, respectively. In month 3 and 6, there was no difference between the two groups(P>0.05). In month 9, 12, 15 and 18, the score was significantly lower in the IDE group than in the routine group(P<0.05). ② In month 3, 6, 9, 12, 15 and 18 after treatment, the score of UPDRS-III(off-stimulation) in the IDE group versus that in the routine group was 23.09±8.63 vs 19.85±7.20, 21.10±7.13 vs 19.63±6.85, 19.30±6.24 vs 19.13±6.57, 17.39±5.37 vs 18.32±6.28, 15.65±4.78 vs 17.35±5.97 and 14.05±4.25 vs 16.10±5.64, respectively. In month 3, 6, 9 and 12, there was no difference between the two groups(P>0.05). In month 15 and 18, the score was significantly lower in the IDE group than in the routine group(P<0.05). ③ In month 3, 6, 9, 12, 15 and 18 after treatment, the MOCA score in the IDE group versus that in the routine group was 21.68±4.59 vs 22.13±4.64, 23.02±3.60 vs 22.69±4.23, 24.39±2.66 vs 23.40±3.69, 25.30±2.12 vs 24.20±3.18, 25.94±1.81 vs 25.17±2.66 and 24.72±2.23 vs 24.27±2.94, respectively. In month 3, 6 and 18, there was no significant difference between the two groups(P>0.05). In month 9, 12 and 15, the score was significantly higher in the IDE group than in the routine group(P<0.05). ④ In month 3, 6, 9, 12, 15 and 18 after treatment, the PSQI score in the IDE group versus that in the routine group was 6.36±4.26 vs 6.12±4.19, 5.33±3.84 vs 5.25±3.85, 4.59±3.45 vs 4.50±3.50, 3.32±2.92 vs 3.51±3.27, 2.71±2.38 vs 3.26±3.03 and 2.20±2.02 vs 3.04±2.84, respectively. In month 3, 6, 9, 12 and 15, there was no difference between the two groups(P>0.05). In month 18, the score was significantly lower in the IDE group than in the routine group(P<0.05). ⑤ In month 3, 6, 9, 12, 15 and 18 after treatment, the NMSS score in the IDE group versus that in the routine group was 54.6±31.87 vs 54.56±33.26, 52.01±30.11 vs 52.42±32.02, 46.84±30.76 vs 50.38±30.65, 41.20±29.60 vs 46.97±28.05, 38.77±26.67 vs 43.18±24.65, 36.63±25.39 vs 41.03±23.48, respectively. There was no significant difference between the two groups(P>0.05). ⑥ In month 6, 12 and 18 after treatment, the level of uric acid in the IDE group versus the routine group was(253.81±111.86) vs(217.82±103.24) μmol/L,(272.56±111.04) vs(198.90±102.36) μmol/L, and(280.12±111.09) μmol/L vs(191.97±101.81) μmol/L, respectively. The level of uric acid was significantly higher in the IDE group than in the routine group(P<0.05). ⑦ In month 6, 12 and 18, the SOD level in the IDE group versus that in the routine group was(154.45±39.96) vs(126.47±41.30) U/mL,(162.45±42.08) vs(119.36±39.71) U/mL, and(172.90±41.78) vs(112.17±37.17) U/mL, respectively. The SOD level was significantly higher in the IDE group than in the routine group(P<0.05). Conclusion IDE can improve the motor and non-motor symptoms in PD patients and slow down the progression of the disease. It has a certain neuroprotective effect on PD.
引文
[1] Sarkar S, Raymick J. Neuroprotective and Therapeutic Strategies against Parkinson?s Disease: Recent Perspectives[J]. Int J Mol Sci, 2016, 17(6): 904.
[2] Liu Y, Schubert DR. The specificity of neuroprotection by antioxidants[J]. J Biomed Sci, 2009, 16(1): 98-111.
[3] Bentinger M, Tekle M. Coenzyme Q-biosynthesis and functions[J]. Biochem Biophys Res Commun, 2010, 396(1): 74-79.
[4] Geromel V, Darin N, Chrétien D, et al. Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits[J]. Mol Genet Metab, 2002, 77(1-2):21-30.
[5] Leonardi A, Crasci' L, Panico A. Antioxidant activity of idebenone-loaded neutral and cationic solid-lipid nanoparticles[J]. Pharm Dev Technol, 2015, 20(6): 716-723.
[6] 崔亚欢, 陈乃耀. 帕金森病的发病机制研究[J]. 中华老年心脑血管病杂志, 2019, 21(1): 106-110.
[7] 陈东万, 曹红元, 严家川, 等. 帕金森病患者血清氧化应激标志物的变化特点[J]. 现代生物医学进展, 2015, 15(34): 6671-6674.CHEN Dongwan, CAO Hongyuan, YAN Jiachuan, et al. Characteristics of oxidative stress biomarkers in serum of patients with Parkinson?s disease[J]. Progress in Modern Biomedicine, 2015, 15(34): 6671-6674.
[8] 王引明, 孔亮, 胡玲玲. 帕金森病患者尿酸、超氧化物歧化酶和血清营养指标的变化[J]. 中国现代药物应用, 2013, 7(23): 76-77.
[9] 李晓鹏, 赵鹏, 钱进. 血尿酸与帕金森病的相关性及其作用机制研究进展[J]. 神经损伤与功能重建, 2018, 13(9): 464-466.
[10] 雷革胜, 苗建亭, 李柱一. 帕金森病血抗氧化系统变化及L-多巴的影响[J]. 中国神经免疫学和神经病学杂志, 2002, 9(3): 172-173, 176.LEI Gesheng, MIAO Jianting, Li Zhuyi. The change of blood antioxidant system in parkinson disease and the influence of L-dopa[J]. Chinese Journal of Neuroimmunology and Neurology, 2002, 9(3): 172-173, 176.
[11] 许继平, 李玉莲, 蔺新英, 等. 帕金森病患者血液抗氧化功能的变化及多巴制剂与Vit E对其影响的研究[J]. 中风与神经疾病杂志, 2000, 17(1): 46-48.XU Jiping, LI Yulian, LIN Xinying, et al. The change of blood antioxidant function in Parkinson disease and the effect of Dopa and Vit E on it[J]. Journal of Apoplexy and Nervous Diseases, 2000, 17(1): 46-48.
[12] 王丽君, 罗蔚锋, 王恒会, 等. 帕金森病患者血尿酸水平[J]. 中华神经科杂志, 2008, 41(3): 157-158.
[13] Rhodes SL, Buchanan DD, Ahmed I, et al. Pooled analysis of iron-related genes in Parkinson?s disease: association with transferring[J]. Neurobiol Dis, 2014, 62(2): 172-178.
[14] Annanmaki T, Pessala-Driver A, Hokkanen L, et al. Uric acid associates with cognition in Parkinson?s disease[J]. Parkinsonism Relat Disord, 2008, 14(7): 576-578.
[15] Schwarzschild MA, Schwid SR, Marek K, et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease[J]. Arch Neurol, 2008, 65(6): 716-723.
[16] 王大勇. 血清尿酸水平与帕金森病运动障碍及左旋多巴治疗的效果观察[J]. 中国实用医药, 2018, 13(17): 141-142.
[17] Martignoni E, Blandini F, Godi L, et al. Peripheral markers of oxidative stress in Parkinson?s disease the role of L-DOPA[J]. Free Radic Biol Med, 1999, 27(3-4): 428-437.
[18] Wieland E, Schütz E, Armstrong VW, et al. Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions[J]. Transplantation, 1995, 60(5): 444-451.
[19] Parkinson MH, Schulz JB, Giunti P. Co-enzyme Q10 and idebenone use in Friedreich?s ataxia[J]. J Neurochem, 2013, 126 (Suppl 1): 125-141.
[20] Gillis JC, Benefield P. Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders[J]. Drugs Aging, 1994, 5(2): 133-152.
[21] Curti D, Izzo E, Brambilla L, et al. Effect of a ubiquinone-like molecule on oxidative energy metabolism in rat cortical synaptosomes at different ages[J]. Neurochem Res, 1995, 20(9): 1001-1006.
[22] Sterky FH, Hoffman AF, Milenkovic D, et al. Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons[J]. Hum Mol Genet, 2012, 21(5): 1078-1089.
[23] Horvath TL, Diano S, Leranth C, et al. Coenzyme Q induces nigral mitochondrial uncoupling and prevents dopamine cell loss in a primate model of Parkinson?s disease[J]. Endocrinology, 2003, 144(7): 2757-2760.
[24] Yan A, Liu Z, 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.
[25] Di Prospero NA, Baker A, Jeffries N. Neurological effects of high-dose idebenone in patients with Friedreich?s ataxia: a randomised, placebo-controlled trial[J]. Lancet Neurol, 2007, 6(10): 878-886.
[2] Liu Y, Schubert DR. The specificity of neuroprotection by antioxidants[J]. J Biomed Sci, 2009, 16(1): 98-111.
[3] Bentinger M, Tekle M. Coenzyme Q-biosynthesis and functions[J]. Biochem Biophys Res Commun, 2010, 396(1): 74-79.
[4] Geromel V, Darin N, Chrétien D, et al. Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits[J]. Mol Genet Metab, 2002, 77(1-2):21-30.
[5] Leonardi A, Crasci' L, Panico A. Antioxidant activity of idebenone-loaded neutral and cationic solid-lipid nanoparticles[J]. Pharm Dev Technol, 2015, 20(6): 716-723.
[6] 崔亚欢, 陈乃耀. 帕金森病的发病机制研究[J]. 中华老年心脑血管病杂志, 2019, 21(1): 106-110.
[7] 陈东万, 曹红元, 严家川, 等. 帕金森病患者血清氧化应激标志物的变化特点[J]. 现代生物医学进展, 2015, 15(34): 6671-6674.CHEN Dongwan, CAO Hongyuan, YAN Jiachuan, et al. Characteristics of oxidative stress biomarkers in serum of patients with Parkinson?s disease[J]. Progress in Modern Biomedicine, 2015, 15(34): 6671-6674.
[8] 王引明, 孔亮, 胡玲玲. 帕金森病患者尿酸、超氧化物歧化酶和血清营养指标的变化[J]. 中国现代药物应用, 2013, 7(23): 76-77.
[9] 李晓鹏, 赵鹏, 钱进. 血尿酸与帕金森病的相关性及其作用机制研究进展[J]. 神经损伤与功能重建, 2018, 13(9): 464-466.
[10] 雷革胜, 苗建亭, 李柱一. 帕金森病血抗氧化系统变化及L-多巴的影响[J]. 中国神经免疫学和神经病学杂志, 2002, 9(3): 172-173, 176.LEI Gesheng, MIAO Jianting, Li Zhuyi. The change of blood antioxidant system in parkinson disease and the influence of L-dopa[J]. Chinese Journal of Neuroimmunology and Neurology, 2002, 9(3): 172-173, 176.
[11] 许继平, 李玉莲, 蔺新英, 等. 帕金森病患者血液抗氧化功能的变化及多巴制剂与Vit E对其影响的研究[J]. 中风与神经疾病杂志, 2000, 17(1): 46-48.XU Jiping, LI Yulian, LIN Xinying, et al. The change of blood antioxidant function in Parkinson disease and the effect of Dopa and Vit E on it[J]. Journal of Apoplexy and Nervous Diseases, 2000, 17(1): 46-48.
[12] 王丽君, 罗蔚锋, 王恒会, 等. 帕金森病患者血尿酸水平[J]. 中华神经科杂志, 2008, 41(3): 157-158.
[13] Rhodes SL, Buchanan DD, Ahmed I, et al. Pooled analysis of iron-related genes in Parkinson?s disease: association with transferring[J]. Neurobiol Dis, 2014, 62(2): 172-178.
[14] Annanmaki T, Pessala-Driver A, Hokkanen L, et al. Uric acid associates with cognition in Parkinson?s disease[J]. Parkinsonism Relat Disord, 2008, 14(7): 576-578.
[15] Schwarzschild MA, Schwid SR, Marek K, et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease[J]. Arch Neurol, 2008, 65(6): 716-723.
[16] 王大勇. 血清尿酸水平与帕金森病运动障碍及左旋多巴治疗的效果观察[J]. 中国实用医药, 2018, 13(17): 141-142.
[17] Martignoni E, Blandini F, Godi L, et al. Peripheral markers of oxidative stress in Parkinson?s disease the role of L-DOPA[J]. Free Radic Biol Med, 1999, 27(3-4): 428-437.
[18] Wieland E, Schütz E, Armstrong VW, et al. Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions[J]. Transplantation, 1995, 60(5): 444-451.
[19] Parkinson MH, Schulz JB, Giunti P. Co-enzyme Q10 and idebenone use in Friedreich?s ataxia[J]. J Neurochem, 2013, 126 (Suppl 1): 125-141.
[20] Gillis JC, Benefield P. Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders[J]. Drugs Aging, 1994, 5(2): 133-152.
[21] Curti D, Izzo E, Brambilla L, et al. Effect of a ubiquinone-like molecule on oxidative energy metabolism in rat cortical synaptosomes at different ages[J]. Neurochem Res, 1995, 20(9): 1001-1006.
[22] Sterky FH, Hoffman AF, Milenkovic D, et al. Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons[J]. Hum Mol Genet, 2012, 21(5): 1078-1089.
[23] Horvath TL, Diano S, Leranth C, et al. Coenzyme Q induces nigral mitochondrial uncoupling and prevents dopamine cell loss in a primate model of Parkinson?s disease[J]. Endocrinology, 2003, 144(7): 2757-2760.
[24] Yan A, Liu Z, 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.
[25] Di Prospero NA, Baker A, Jeffries N. Neurological effects of high-dose idebenone in patients with Friedreich?s ataxia: a randomised, placebo-controlled trial[J]. Lancet Neurol, 2007, 6(10): 878-886.