Blin O, Desnuelle C, Rascol O, Borg M, Peyro Saint Paul H, Azulay J P, Billé F, Figarella D, Coulom F, Pellissier J F
Pharmacologie Médicale et Clinique, CHU Timone, Marseille, France.
J Neurol Sci. 1994 Aug;125(1):95-101. doi: 10.1016/0022-510x(94)90248-8.
We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Dopa-treated PD patients and 6 de novo patients), 5 patients with multiple system atrophy (MSA) and from 43 age-matched controls in order to determine the occurrence of mitochondrial respiratory chain abnormalities in parkinsonian syndromes. In our control subjects, we found a significant age-related decrease in the activity of respiratory chain complex I. As compared to carefully age-matched control subjects, activity of complex (NADH:ubiquinone reductase) was significantly lower in muscle mitochondria from patients with PD and MSA and a mean remaining activity < 30% of controls was observed. Mean activities of complexes III (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) were also lower in PD patients than controls, but a low activity (remaining activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succinate:ubiquinone reductase) was observed. Our results support the hypothesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related deficiency. This deficit can be found in de novo PD patients as well as in treated patients. The observed respiratory enzyme chain deficiency could not be explained by the dose and duration of L-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters and enzyme complexes activities.
我们研究了27例特发性帕金森病（PD；21例接受多巴治疗的PD患者和6例初发患者）、5例多系统萎缩（MSA）患者以及43例年龄匹配的对照者骨骼肌中的线粒体呼吸链功能，以确定帕金森综合征中线粒体呼吸链异常的发生率。在我们的对照受试者中，我们发现呼吸链复合体I的活性随年龄显著降低。与年龄精确匹配的对照受试者相比，PD和MSA患者肌肉线粒体中复合体I（NADH：泛醌还原酶）的活性显著降低，观察到平均剩余活性<对照者的30%。PD患者中复合体III（泛醇：细胞色素c还原酶）和复合体IV（细胞色素c氧化酶）的平均活性也低于对照者，但仅在5例PD患者中观察到复合体I和III或I和IV的活性较低（剩余活性<对照者的30%）。未观察到复合体II（琥珀酸：泛醌还原酶）活性缺乏。我们的结果支持这样的假设，即与显示出与年龄相关缺乏的年龄匹配对照者相比，PD和MSA中广泛存在线粒体复合体I缺乏。这种缺乏在初发PD患者以及接受治疗的患者中均能发现。观察到的呼吸酶链缺乏不能用左旋多巴或多巴胺能激动剂治疗的剂量和持续时间、疾病严重程度、焦虑或抑郁来解释，因为在这些参数与酶复合体活性之间未发现显著相关性。
