目前服用他汀類藥物治療高膽固醇癥的病人或許會存在肌肉疼痛，近日，來自哥本哈根大學的研究者發(fā)現了病人出現肌肉疼痛癥狀的內在機制，相關研究成果刊登在了國際雜志Journal of American College of Cardiology上。

    他汀類藥物（statin）是一類通過抑制肝臟產生膽固醇的能力來治療血液中高膽固醇的藥物，其是市場上最有潛力的降低低密度脂蛋白的藥物，目前將近有600，000名丹麥人每天服用該類藥物來治療高膽固醇癥。

    研究者Flemming Dela教授表示，我們都知道服用他汀類藥物會引發(fā)肌肉疼痛，而且有75%的病人都經歷著疼痛的折磨，如今我們的研究揭示了他汀類藥物療法可以影響肌肉能量的產生，這或許是直接導致病人肌肉虛弱和疼痛的原因。

    研究中，研究者同樣揭示了進行他汀類藥物療法的患者體內或許關鍵蛋白Q10的水平較低，肌肉中Q10的好進以及隨既而來的低能量產生會許是引發(fā)許多病人肌肉疼痛的主要原因。在丹麥大約40%的病人進行他汀類藥物療法稱為mono療法，而且這僅僅是患高膽固醇病人使用的療法，而且這些病人并沒有其它影響心臟健康的風險因素。

    在研究中，研究者以患者他汀類藥物療法為視角調查了其對病人的影響，結果發(fā)現接受他汀類藥物療法的病人，使用該療法會影響其機體肌肉的能量代謝，從而導致患者出現肌肉疼痛癥狀，這就為研究者深入研究其發(fā)病機制提供了思路和線索。

    Simvastatin Effects on Skeletal Muscle : Relation to Decreased Mitochondrial Function and Glucose Intolerance

    Objectives: Glucose tolerance and skeletal muscle coenzyme Q10 (Q10) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9).

    Background: A prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q10 may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism.

    Methods: Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q10 content was determined.

    Results: Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q10 content was reduced (p = 0.05), whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I– and complex II–linked substrates were used alone, but when complex I + II–linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased (p < 0.01) capacity was observed in the patients compared with the control subjects.

    Conclusions: These simvastatin-treated patients were glucose intolerant. A decreased Q10 content was accompanied by a decreased maximal OXPHOS capacity in the simvastatin-treated patients. It is plausible that this finding partly explains the muscle pain and exercise intolerance that many patients experience with their statin treatment.