Du Wei, Su Jinyu, Ye Dan, Wang Yuegang, Huang Qiaobing, Gong Xiaowei
* Department of Pathophysiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
‡ Respiratory Diseases Group, the 6th Unit, Department of Internal Medicine, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
Am J Chin Med. 2016;44(5):1027-41. doi: 10.1142/S0192415X16500579. Epub 2016 Jul 19.
Inhaled corticosteroids (ICS) are widely used to manage chronic obstructive pulmonary disease (COPD). However, withdrawal of ICS generally causes various adverse effects, warranting careful management of the ICS withdrawal. Pinellia ternata, a traditional Chinese herbal medicine, has been used to treat respiratory diseases in China for centuries. Here, we investigated its role in antagonizing ICS withdrawal-induced side effects, and explored the underlying mechanisms. The rat COPD model was established using a combination of passive cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS). COPD rats were treated with saline or budesonide inhalation, or with budesonide inhalation followed by saline inhalation or Pinellia ternata gavage. The number of goblet cells and the level of mucin 5AC (MUC5AC) were enhanced by budesonide withdrawal. Pinellia ternata treatment significantly blocked these effects. Further, Pinellia ternata treatment reversed budesonide withdrawal-induced increase of interleukin 1[Formula: see text] (IL-1[Formula: see text] and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) levels in bronchoalveolar lavage fluid (BALF). Extracellular signal-regulated kinase (ERK), but neither p38 nor c-Jun N-terminal kinase (JNK), was activated by budesonide withdrawal, and the activation was blocked by Pinellia ternata treatment. The MUC5AC expression was positively correlated with goblet cell number, IL-1[Formula: see text] and TNF-[Formula: see text] levels, and ERK activity. Pinellia ternata treatment protected the airway from ICS withdrawal-induced mucus hypersecretion and airway inflammation by inhibiting ERK activation. Pinellia ternata treatment may represent a novel therapeutic strategy to prevent ICS withdrawal-induced side effects in COPD patients.
吸入性糖皮质激素（ICS）被广泛用于治疗慢性阻塞性肺疾病（COPD）。然而，停用ICS通常会引起各种不良反应，因此需要谨慎管理ICS的撤药过程。半夏是一种传统的中草药，在中国用于治疗呼吸道疾病已有数百年历史。在此，我们研究了其在拮抗ICS撤药引起的副作用中的作用，并探讨了潜在机制。采用被动吸烟和气管内滴注脂多糖（LPS）相结合的方法建立大鼠COPD模型。COPD大鼠分别用生理盐水或布地奈德吸入治疗，或先吸入布地奈德，然后吸入生理盐水或进行半夏灌胃。停用布地奈德会增加杯状细胞数量和粘蛋白5AC（MUC5AC）水平。半夏治疗可显著阻止这些效应。此外，半夏治疗可逆转停用布地奈德引起的支气管肺泡灌洗液（BALF）中白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）水平的升高。停用布地奈德可激活细胞外信号调节激酶（ERK），但不激活p38或c-Jun氨基末端激酶（JNK），而半夏治疗可阻断这种激活。MUC5AC表达与杯状细胞数量、IL-1β和TNF-α水平以及ERK活性呈正相关。半夏治疗通过抑制ERK激活，保护气道免受ICS撤药引起的黏液分泌过多和气道炎症。半夏治疗可能是预防COPD患者ICS撤药引起副作用的一种新的治疗策略。
