综述:Rho激酶作为治疗哮喘和慢性阻塞性肺疾病的治疗靶点

L. Fernandes, P. Henry, R. Goldie
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引用次数: 17

摘要

哮喘是一种复杂的气道炎症性疾病,涉及可逆性支气管收缩。慢性阻塞性肺疾病的典型特征是炎症和气流限制,具有不可逆的成分。现在有大量证据表明,Rho激酶参与了许多与这些呼吸道疾病相关的病理通路,包括支气管收缩、气道炎症、气道重塑、神经调节和呼吸道病毒感染引起的恶化。事实上,Rho激酶抑制剂Y-27632可引起支气管扩张,减少肺嗜酸性粒细胞的转运和气道高反应性。此外,越来越多的证据表明,抑制Rho激酶可能通过调节其他几个系统和过程,对哮喘和COPD的症状和疾病进展产生重大有益影响。因此,Rho激酶途径可能确实是治疗哮喘和慢性阻塞性肺疾病的一个有价值的治疗靶点。
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Review: Rho kinase as a therapeutic target in the treatment of asthma and chronic obstructive pulmonary disease
Asthma is a complex inflammatory disease of the airways involving reversible bronchoconstriction. Chronic obstructive pulmonary disease is typified by inflammation and airflow limitation that has an irreversible component. There is now substantial evidence that Rho kinase is involved in many of the pathways that contribute to the pathologies associated with these respiratory diseases including bronchoconstriction, airway inflammation, airway remodelling, neuromodulation and exacerbations due to respiratory tract viral infection. Indeed the Rho kinase inhibitor Y-27632 causes bronchodilatation and reduces pulmonary eosinophilia trafficking and airways hyperresponsiveness. Furthermore, accumulating evidence suggests that inhibition of Rho kinase could have a major beneficial impact on symptoms and disease progression in asthma and COPD by modulating several other systems and processes. Thus, the Rho kinase pathway may indeed be a worthwhile therapeutic target in the treatment of asthma and chronic obstructive pulmonary disease.
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