Davis Max E, Korn Michael A, Gumucio Jonathan P, Harning Julie A, Saripalli Anjali L, Bedi Asheesh, Mendias Christopher L
Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
J Shoulder Elbow Surg. 2015 Feb;24(2):280-7. doi: 10.1016/j.jse.2014.06.048. Epub 2014 Sep 9.
Chronic rotator cuff tears are a common source of shoulder pain and disability, and patients with chronic cuff tears often have substantial weakness, fibrosis, inflammation, and fat accumulation. Identifying therapies to prevent the development of these pathologic processes will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated anti-inflammatory and antifibrotic effects in many tissues but had not previously been studied in the context of rotator cuff tears. We hypothesized that after the induction of a massive supraspinatus tear, simvastatin would protect muscles from a loss of force production and fibrosis.
We measured changes in muscle fiber contractility, histology, and biochemical markers of fibrosis and fatty infiltration in rats that received a full-thickness supraspinatus tear and were treated with either carrier alone or simvastatin.
Compared with vehicle-treated controls, simvastatin did not have an appreciable effect on muscle fiber size, but treatment did increase muscle fiber specific force by 20%. Simvastatin also reduced collagen accumulation by 50% but did not affect triglyceride content of muscles. Several favorable changes in the expression of genes and other markers of inflammation, fibrosis, and regeneration were also observed.
Simvastatin partially protected muscles from the weakness that occurs as a result of chronic rotator cuff tear. Fibrosis was also markedly reduced in simvastatin-treated animals. Whereas further studies are necessary, statin medication could potentially help improve outcomes for patients with rotator cuff tears.
慢性肩袖撕裂是肩部疼痛和功能障碍的常见原因,慢性肩袖撕裂患者常伴有明显的肌肉无力、纤维化、炎症和脂肪堆积。确定预防这些病理过程发展的治疗方法可能会对临床结果产生积极影响。辛伐他汀是一种在许多组织中已显示出抗炎和抗纤维化作用的药物,但此前尚未在肩袖撕裂的背景下进行研究。我们假设在诱导巨大的冈上肌撕裂后,辛伐他汀将保护肌肉免受力量产生丧失和纤维化的影响。
我们测量了接受全层冈上肌撕裂并接受单独载体或辛伐他汀治疗的大鼠的肌纤维收缩性、组织学以及纤维化和脂肪浸润的生化标志物的变化。
与载体治疗的对照组相比,辛伐他汀对肌纤维大小没有明显影响,但治疗确实使肌纤维比力增加了20%。辛伐他汀还使胶原蛋白积累减少了50%,但不影响肌肉的甘油三酯含量。还观察到炎症、纤维化和再生的基因表达及其他标志物的一些有利变化。
辛伐他汀部分保护肌肉免受慢性肩袖撕裂导致的无力影响。在辛伐他汀治疗的动物中,纤维化也明显减少。虽然还需要进一步研究,但他汀类药物可能有助于改善肩袖撕裂患者的预后。