Angiotensin receptor blockade mimics the effect of exercise on recovery after orthopaedic trauma by decreasing pain and improving muscle regeneration.
Angiotensin receptor blockade mimics the effect of exercise on recovery after orthopaedic trauma by decreasing pain and improving muscle regeneration.
复制标题
血管紧张素受体阻断模仿运动对骨科创伤后恢复的影响，通过减轻疼痛和改善肌肉再生。
DOI：
10.1113/jp278991
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Clark JD
中科院分区：
文献类型：
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作者：
Tawfik VL;Quarta M;Paine P;Forman TE;Pajarinen J;Takemura Y;Goodman SB;Rando TA;Clark JD
肢体损伤后的慢性疼痛和残疾是主要的公共卫生问题。损伤后的早期活动可以改善患者的功能结局，尽管何时以及如何实施康复策略仍然是一个临床挑战。此外，运动的有益效果是否可以使用药理学工具重现仍然是未知的，并可能使那些由于固定而无法运动的患者受益。我们建立了一种胫骨骨折和针固定合并肌肉损伤的骨科创伤小鼠模型。行为测量包括机械伤害性阈值和在运动轮上跑步的距离。骨愈合进行了量化，使用微计算机断层扫描，肌纤维的大小分布和纤维化，然后使用免疫组织化学。我们发现该模型提供了强大的机械性异常性疼痛、纤维化以及从受伤后持续长达5周的平均肌纤维尺寸变小的转变。我们还观察到，允许“晚期”（1-2周）而不是“早期”（0-1周）运动后，受伤导致更大的整体跑步活动和更大的逆转异常性疼痛。与此同时，晚跑模式与肌肉纤维化减少、肌纤维直径提前增加以及减少骨痂体积的短期益处有关。在饮用水中给小鼠提供抗纤维化血管紧张素受体阻断剂氯沙坦，可以减少异常性疼痛和肌肉纤维化。联合使用氯沙坦和晚锻炼没有额外的好处。我们的结论是，在开始运动之前，必须允许骨科创伤后的早期愈合，以达到最佳的疼痛，功能和生理结果，氯沙坦是一个可行的候选翻译研究。
Chronic pain and disability after limb injury are major public health problems. Early mobilization after injury improves functional outcomes for patients, although when and how to implement rehabilitation strategies remains a clinical challenge. Additionally, whether the beneficial effects of exercise can be reproduced using pharmacological tools remains unknown and may benefit patients who are unable to exercise as a result of immobilization. We developed a murine model of orthopaedic trauma combining tibia fracture and pin fixation with muscle damage. Behavioural measures included mechanical nociceptive thresholds and distances run on exercise wheels. Bone healing was quantified using microcomputed tomagraphic scanning, and muscle fibre size distribution and fibrosis were followed using immunohistochemistry. We found that the model provided robust mechanical allodynia, fibrosis and a shift to smaller average muscle fibre size lasting up to 5 weeks from injury. We also observed that allowing ‘late’ (weeks 1–2) rather than ‘early’ (weeks 0–1) exercise after injury resulted in greater overall running activity and greater reversal of allodynia. In parallel, the late running paradigm was associated with reduced muscle fibrosis, earlier increase in muscle fibre diameter and a short-term benefit in reducing callus volume. Providing the anti-fibrotic angiotensin receptor blocker losartan to mice in drinking water reduced both allodynia and muscle fibrosis. Combining losartan and late exercise provided no additional benefit. We conclude that early healing after orthopaedic trauma must be allowed prior to the initiation of exercise to achieve optimal pain, functional and physiological outcomes and that losartan is a viable candidate for translational studies.