Hansen Michelle J, Gualano Rosa C, Bozinovski Steve, Vlahos Ross, Anderson Gary P
Lung Disease Research Laboratory, Department of Pharmacology, Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Victoria 3010, Australia.
Pharmacol Ther. 2006 Jan;109(1-2):162-72. doi: 10.1016/j.pharmthera.2005.06.007. Epub 2005 Sep 12.
Chronic obstructive pulmonary disease (COPD) is an incurable group of lung diseases characterised by progressive airflow limitation and loss of lung function, which lead to profound disability. It is mostly caused by cigarette smoke. Although COPD is one of the most prevalent diseases worldwide and its incidence is increasing, current therapies do little to improve the condition. Much current research focuses on strategies to halt the accelerated rate of decline in lung function that occurs in the disease. However, as most symptoms occur when the lungs are already extensively and irreversibly damaged, it is uncertain whether an agent able to slow or halt decline in lung function would actually provide relief to COPD patients. As lung function worsens, systemic comorbidities contribute markedly to disability. Loss of lean body mass (skeletal muscle) has recently been identified as a major determinant of disability in COPD and an independent predictor of mortality. In contrast to lung structure damage, skeletal muscle retains regenerative capacity in COPD. In this review, we discuss mechanisms of wasting in COPD, focusing on therapeutic strategies that might improve the health and productive life expectancy of COPD patients by improving skeletal muscle mass and function. Single or combination approaches exploiting the suppression of procatabolic inflammatory mediators, inhibition of ubiquitin ligases, repletion of anabolic hormones and growth factors, inhibition of myoblast apoptosis, remediation of systemic oxidative stress and promotion of repair, and regeneration via stimulation of satellite cell differentiation hold considerable therapeutic promise.
慢性阻塞性肺疾病（COPD）是一组无法治愈的肺部疾病，其特征为进行性气流受限和肺功能丧失，可导致严重残疾。该病主要由吸烟引起。尽管COPD是全球最常见的疾病之一，且发病率不断上升，但目前的治疗方法对改善病情作用甚微。当前许多研究聚焦于阻止该疾病中出现的肺功能加速下降的策略。然而，由于大多数症状在肺部已经受到广泛且不可逆的损害时才出现，因此能够减缓或阻止肺功能下降的药物是否真的能缓解COPD患者的症状尚不确定。随着肺功能恶化，全身性合并症对残疾的影响显著。瘦体重（骨骼肌）的丧失最近被确定为COPD患者残疾的主要决定因素和死亡率的独立预测指标。与肺结构损伤不同，骨骼肌在COPD中仍保留再生能力。在本综述中，我们讨论COPD中消瘦的机制，重点关注可能通过改善骨骼肌质量和功能来提高COPD患者健康水平和预期寿命的治疗策略。利用抑制促分解代谢炎症介质、抑制泛素连接酶、补充合成代谢激素和生长因子、抑制成肌细胞凋亡、纠正全身性氧化应激以及通过刺激卫星细胞分化促进修复和再生的单一或联合方法具有可观的治疗前景。
