Laaksonen R, Jokelainen K, Laakso J, Sahi T, Harkonen M, Tikkanen M J, Himberg J J
Department of Clinical Pharmacology, University of Helskini, Finland.
Am J Cardiol. 1996 Apr 15;77(10):851-4. doi: 10.1016/S0002-9149(97)89180-1.
It has been hypothesized that treating hypercholesterolemic patients with statins will lead not only to a reduction in cholesterol, but also to inhibited synthesis of other compounds which derive from the synthetic pathway of cholesterol. In theory, this could further lead to ubiquinone deficiency in muscle cell mitochondria, disturbing normal cellular respiration and causing adverse effects such as rhabdomyolysis. Furthermore, ubiquinone is one of the lipophilic antioxidants in low-density lipoprotein (LDL), and therefore it has also been hypothesized that statin treatment will reduce the antioxidant capacity of LDL. We investigated the effect of 6 months of simvastatin treatment (20 mg/day) on skeletal muscle concentrations of high-energy phosphates and ubiquinone by performing biopsies in 19 hypercholesterolemic patients. Parallel assays were performed in untreated control subjects. The muscle high-energy phosphate and ubiquinone concentrations assayed after simvastatin treatment were similar to those observed at baseline and did not differ from the values obtained in control subjects at the beginning and end of follow-up. These results do not support the hypothesis of diminished isoprenoid synthesis or energy generation in muscle cells during simvastatin treatment. Furthermore, the results of analysis of antioxidant concentrations in LDL before and after simvastatin treatment indicate that the antioxidant capacity of LDL is maintained in simvastatin-treated patients.
有假说认为，用他汀类药物治疗高胆固醇血症患者不仅会使胆固醇降低，还会抑制其他源自胆固醇合成途径的化合物的合成。从理论上讲，这可能会进一步导致肌肉细胞线粒体中泛醌缺乏，扰乱正常的细胞呼吸并引起诸如横纹肌溶解等不良反应。此外，泛醌是低密度脂蛋白（LDL）中的亲脂性抗氧化剂之一，因此也有假说认为他汀类药物治疗会降低LDL的抗氧化能力。我们通过对19例高胆固醇血症患者进行活检，研究了辛伐他汀治疗6个月（20毫克/天）对骨骼肌中高能磷酸盐和泛醌浓度的影响。在未经治疗的对照受试者中进行了平行测定。辛伐他汀治疗后测定的肌肉高能磷酸盐和泛醌浓度与基线时观察到的浓度相似，并且与随访开始和结束时在对照受试者中获得的值没有差异。这些结果不支持辛伐他汀治疗期间肌肉细胞中类异戊二烯合成或能量产生减少的假说。此外，辛伐他汀治疗前后LDL中抗氧化剂浓度的分析结果表明，辛伐他汀治疗的患者中LDL的抗氧化能力得以维持。
