Oliveira L P, Vieira C P, Marques P P, Pimentel E R
a Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, SP, Brazil.
b Department of Pharmacology, Medical Sciences College, University of Campinas - UNICAMP, Campinas, SP, Brazil.
Can J Physiol Pharmacol. 2017 Apr;95(4):333-339. doi: 10.1139/cjpp-2016-0133. Epub 2016 Oct 4.
Over the past few years, a number of cases of tendon injuries associated with statin therapy have been reported. In this study, we assessed whether statins can affect the extracellular matrix (ECM) of the deep digital flexor tendon (DDFT) and patellar tendon (PT). Wistar rats were assigned to groups treated with atorvastatin (A20, A80), treated with simvastatin (S20, S80), and control. Zymography, Western blotting for collagen I, non-collagenous proteins (NCP), glycosaminoglycans (GAGs), and hydroxyproline quantifications were performed. DDFT findings: NCP were increased in A20 and A80; higher concentration of hydroxyproline was found in S80; levels of GAGs was increased in all statin-treated groups; collagen I was increased in S80 and pro-MMP-2 activity was reduced in A80, S20, and S80. PT findings: NCP were reduced in A20, A80, and S80; GAGs was reduced in A80 and S20; collagen I was increased in A20 and pro-MMP-2 activity was reduced in the S20. Both the statins provoked marked changes in both tendons. All these changes may make the tendons more prone to microdamage and ruptures. Therefore, a better understanding of the behavior of the tendon ECM components under statin therapy may provide important insights into the mechanisms behind statin-induced tendon injuries.
在过去几年中，已有多例与他汀类药物治疗相关的肌腱损伤病例报道。在本研究中，我们评估了他汀类药物是否会影响指深屈肌腱（DDFT）和髌腱（PT）的细胞外基质（ECM）。将Wistar大鼠分为阿托伐他汀治疗组（A20、A80）、辛伐他汀治疗组（S20、S80）和对照组。进行了酶谱分析、I型胶原蛋白的蛋白质印迹分析、非胶原蛋白（NCP）分析、糖胺聚糖（GAGs）分析以及羟脯氨酸定量分析。DDFT的研究结果：A20和A80组的NCP增加；S80组发现羟脯氨酸浓度更高；所有他汀类药物治疗组的GAGs水平均升高；S80组的I型胶原蛋白增加，A80、S20和S80组的前基质金属蛋白酶-2（pro-MMP-2）活性降低。PT的研究结果：A20、A80和S80组的NCP减少；A80和S20组的GAGs减少；A20组的I型胶原蛋白增加，S20组的pro-MMP-2活性降低。两种他汀类药物均在两条肌腱中引发了显著变化。所有这些变化可能使肌腱更容易发生微损伤和断裂。因此，更好地了解他汀类药物治疗下肌腱ECM成分的行为，可能为他汀类药物诱导的肌腱损伤背后的机制提供重要见解。
