Department of Functional and Structural Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, SP, Brazil.
Toxicology. 2013 Sep 15;311(3):162-8. doi: 10.1016/j.tox.2013.06.010. Epub 2013 Jul 4.
Statins have been widely prescribed as lipid-lowering drugs and are associated with tendon rupture. Therefore, this study aimed to evaluate the possible biochemical changes in the Achilles tendon of rats after chronic treatment with statins. Dosages of statins were calculated using allometric scaling with reference to the 80mg/day and 20mg/day, doses recommended for humans. The rats were divided into the following groups: treated with simvastatin (S-20 and S-80), treated with atorvastatin (A-20 and A-80), and the control group that received no treatment (C). Measurements of low-density lipoprotein (LDL) in the plasma were performed. The levels of non-collagenous proteins, glycosaminoglycans (GAGs) and hydroxyproline were quantified. Western blotting for collagen I was performed, and the presence of metalloproteinases (MMPs)-2 and -9 was investigated through zymography. The concentration of non-collagenous proteins in S-20 was less than the C group. There was a significant increase in pro-MMP-2 activity in A-80 group and in active MMP-2 in S-20 group compared to the C group. A significant increase in latent MMP-9 activity was observed in both the A-80 and S-20 groups when compared to C group. In the A-20 group, there was a lower amount of collagen I in relation to C group. In addition, a higher concentration of hydroxyproline was found in the S-20 group than the C group. The analysis of GAGs showed a significant increase in the A-20 group when compared to C group. The treatment induced remarkable alterations in the Achilles tendon and the response of the tissue seems to depend of the used statin dosage. The presence of MMP-2 and MMP-9 is evidence of the degradation and remodeling processes in the extracellular matrix of the tendons. Our results show that statins induce imbalance of extracellular matrix components and possibly induce microdamage in tendons.
他汀类药物被广泛用作降脂药物，与肌腱断裂有关。因此，本研究旨在评估他汀类药物慢性治疗后大鼠跟腱可能发生的生化变化。他汀类药物的剂量通过与人类推荐的 80mg/天和 20mg/天剂量相关的比例缩放来计算。将大鼠分为以下几组：辛伐他汀治疗组（S-20 和 S-80）、阿托伐他汀治疗组（A-20 和 A-80）和未治疗的对照组（C）。测量血浆中低密度脂蛋白（LDL）。定量测定非胶原蛋白、糖胺聚糖（GAGs）和羟脯氨酸的含量。通过 Western blot 检测 I 型胶原，通过酶谱法研究基质金属蛋白酶（MMPs）-2 和 -9 的存在。S-20 组的非胶原蛋白浓度低于 C 组。与 C 组相比，A-80 组中 pro-MMP-2 活性显著增加，S-20 组中活性 MMP-2 显著增加。与 C 组相比，A-80 和 S-20 组中潜伏 MMP-9 活性均显著增加。与 C 组相比，A-20 组中 I 型胶原的含量较低。此外，S-20 组羟脯氨酸的浓度高于 C 组。GAGs 的分析表明，与 C 组相比，A-20 组有显著增加。该治疗对跟腱产生了显著的影响，组织的反应似乎取决于所使用的他汀类药物剂量。MMP-2 和 MMP-9 的存在证明了细胞外基质的降解和重塑过程。我们的结果表明，他汀类药物诱导细胞外基质成分失衡，并可能导致肌腱微损伤。
