Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis.
Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis.
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DOI：
10.1042/cs20180912
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发表时间：
2019-02
期刊：
影响因子：
6
通讯作者：
Xuhua Yu;H. Seow;Hao Wang;Desiree A. Anthony;S. Bozinovski;Lin Lin-Lin;Ji‐Ming Ye;R. Vlahos
中科院分区：
文献类型：
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作者：
Xuhua Yu;H. Seow;Hao Wang;Desiree A. Anthony;S. Bozinovski;Lin Lin-Lin;Ji‐Ming Ye;R. Vlahos
慢性阻塞性肺疾病（COPD）是一种无法治愈的主要全球健康负担，到2030年将成为世界第三大死亡原因。众所周知，香烟烟雾引起的过度炎症和氧化应激反应（CS）会导致肺气肿、小气道纤维化、粘液分泌过多和进行性气流限制。目前的治疗方法在抑制慢性炎症方面的疗效有限，因此不能逆转引发和驱动疾病长期进展的病理。特别是，目前还没有针对慢性阻塞性肺病的中性粒细胞炎症的有效治疗方法，众所周知，慢性阻塞性肺病可通过包括中性粒细胞弹性酶（NE）在内的一系列蛋白水解酶的脱颗粒导致组织损伤。苦参碱是一种从苦参中提取的生物碱化合物，具有抗炎活性。因此，本研究的目的是研究苦参碱是否能抑制cs诱导的小鼠肺部炎症。苦参碱显著降低小鼠cs诱导的支气管肺泡灌洗液（BALF）中性粒细胞和NE活性。在cs暴露的小鼠中，苦参碱的BALF中性粒细胞的减少不是由于前中性粒细胞细胞因子/趋化因子的减少，而是由于苦参碱引起中性粒细胞凋亡的能力，我们在体外证明了这一点。因此，我们的数据表明苦参碱具有抗炎作用，可能在治疗慢性阻塞性肺疾病中观察到的cs诱导的肺部炎症中具有治疗潜力。
Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion, and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiates and drives the long-term progression of disease. In particular, there are no effective therapeutics that target neutrophilic inflammation in COPD, which is known to cause tissue damage by degranulation of a suite of proteolytic enzymes including neutrophil elastase (NE). Matrine, an alkaloid compound extracted from Sophora flavescens Ait, has well known anti-inflammatory activity. Therefore, the aim of the present study was to investigate whether matrine could inhibit CS-induced lung inflammation in mice. Matrine significantly reduced CS-induced bronchoalveolar lavage fluid (BALF) neutrophilia and NE activity in mice. The reduction in BALF neutrophils in CS-exposed mice by matrine was not due to reductions in pro-neutrophil cytokines/chemokines, but rather matrine's ability to cause apoptosis of neutrophils, which we demonstrated ex vivo Thus, our data suggest that matrine has anti-inflammatory actions that could be of therapeutic potential in treating CS-induced lung inflammation observed in COPD.