Experimental lovastatin myopathy.
Experimental lovastatin myopathy.
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实验性洛伐他汀肌病。
DOI：
10.1097/00005072-199309000-00012
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发表时间：
1993
影响因子：
3.2
通讯作者：
Engel,AG
中科院分区：
文献类型：
--
作者：
Waclawik,AJ;Lindal,S;Engel,AG
洛伐他汀（LS）是一种有效的HMG-CoA抑制剂，用于治疗 高胆固醇血症在人类中，它可以引起严重的坏死性肌病， 肌红蛋白尿和肾衰竭探讨LS诱导的肝细胞癌的发病机制， 我们研究了LS对大鼠骨骼肌的影响。刘易斯大鼠 灌胃1 mg/g体重/天LS。对照大鼠接受 羧甲基纤维素基悬浮液。腓肠肌和比目鱼肌， 分别对快、慢肌群进行光、电观察 显微镜到第10天，LS处理的大鼠变得严重虚弱。腓肠肌 严重影响膜细胞器的退化， 微空泡形成，但比目鱼肌幸免。最终，20-50%的 腓肠肌但比目鱼肌纤维均未坏死。非坏死纤维 显示酸性磷酸酶没有增加，表明自噬不是 兴奋了我们的结论是，LS通过诱导肌肉变性而导致肌肉损伤。 膜细胞器和快速收缩肌纤维是选择性脆弱的 LS肌病。
Lovastatin (LS) is a potent HMG-CoAinhibitor used in the treatment of hypercholesterolemia. In humans it can cause a severe, necrotizing myopathy with myoglobinuriaand renal failure. To investigate the pathogenesis of LS-induced myopathy we studied the effects of LS on rat skeletal muscle. Lewis rats were gavage-fed 1 mg/g body weight/day of LS. Control rats received carboxyrnethylcellulose-based suspension by gavage. Gastrocnemius and soleus, fast and slow twitch muscles respectively, were studied by light and electron microscopy. By day 10 LS-treated rats became severely weak. Gastrocnemius was severely affected with degeneration of membranous organelles and microvacuoleformation, but soleus was spared. Eventually, 20–50% of the gastrocnemius but none of the soleus fibers became necrotic. Non-necrotic fibers showed no increases of acid phosphatase, indicating that autophagy was not excited. We conclude that LS causes muscle injury by inducing degeneration of membranous organelles, and fast twitch muscle fibers are selectively vulnerable to LS myopathy.