Lamperti Costanza, Naini Ali B, Lucchini Valeria, Prelle Alessandro, Bresolin Nereo, Moggio Maurizio, Sciacco Monica, Kaufmann Petra, DiMauro Salvatore
Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Unita' Operativa, Neurologia, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Arch Neurol. 2005 Nov;62(11):1709-12. doi: 10.1001/archneur.62.11.1709.
Statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce the level of cholesterol by inhibiting the synthesis of mevalonate, an intermediary in the cholesterol biosynthetic pathway. Use of statin drugs has been associated with a variety of skeletal muscle-related complaints. Coenzyme Q10 (CoQ10), a component of the mitochondrial respiratory chain, is also synthesized from mevalonate, and decreased muscle CoQ10 concentration may have a role in the pathogenesis of statin drug-related myopathy.
To measure the CoQ10 concentration and respiratory chain enzyme activities in muscle biopsy specimens from 18 patients with statin drug-related myopathy and to look for evidence of apoptosis using the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) assay.
An open-labeled study of CoQ10 concentration in muscle from patients with increased serum creatine kinase concentrations while receiving standard statin drug therapy.
Neuromuscular centers at 2 academic tertiary care hospitals.
Muscle structure was essentially normal in 14 patients and showed evidence of mitochondrial dysfunction and nonspecific myopathic changes in 2 patients each. Muscle CoQ10 concentration was not statistically different between patients and control subjects, but it was more than 2 SDs below the normal mean in 3 patients and more than 1 SD below normal in 7 patients. There was no TUNEL positivity in any patients.
These data suggest that statin drug-related myopathy is associated with a mild decrease in muscle CoQ10 concentration, which does not cause histochemical or biochemical evidence of mitochondrial myopathy or morphologic evidence of apoptosis in most patients.
他汀类药物(3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂)通过抑制甲羟戊酸(胆固醇生物合成途径中的一种中间体)的合成来降低胆固醇水平。他汀类药物的使用与多种骨骼肌相关症状有关。辅酶Q10(CoQ10)是线粒体呼吸链的一个组成部分,也由甲羟戊酸合成,肌肉中CoQ10浓度降低可能在他汀类药物相关性肌病的发病机制中起作用。
测量18例他汀类药物相关性肌病患者肌肉活检标本中的CoQ10浓度和呼吸链酶活性,并使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法(TUNEL法)寻找凋亡证据。
一项对接受标准他汀类药物治疗且血清肌酸激酶浓度升高的患者肌肉中CoQ10浓度的开放标签研究。
2家学术性三级护理医院的神经肌肉中心。
14例患者的肌肉结构基本正常,2例患者的肌肉出现线粒体功能障碍和非特异性肌病改变的证据。患者与对照受试者之间的肌肉CoQ10浓度无统计学差异,但3例患者低于正常均值超过2个标准差,7例患者低于正常均值超过1个标准差。所有患者均未出现TUNEL阳性。
这些数据表明,他汀类药物相关性肌病与肌肉CoQ10浓度轻度降低有关,在大多数患者中,这种降低不会导致线粒体肌病的组织化学或生化证据或凋亡的形态学证据。