Chen Yunkun, Zhang Wenbin
Department of Respiratory and Critical Care Medicine, Chongqing Traditional Chinese Medicine Hospital, No. 40, Daomenkou, Yuzhong District, Chongqing 400011, China.
Evid Based Complement Alternat Med. 2022 May 6;2022:7942623. doi: 10.1155/2022/7942623. eCollection 2022.
Chronic obstructive pulmonary disease (COPD) is a chronic disease with a long course which is often induced by an acute exacerbation of the disease by a respiratory tract infection. We aimed to explore the effect of Zhuye Shigao Decoction combined with Qingqi Huatan Pills on the regulation of the interleukin (IL)-6-mediated JAK1/STAT3 signaling pathway in rats with an acute exacerbation of COPD (phlegm-heat stagnating in the lungs). A model of COPD rats with lung phlegm-heat stagnation was established by smoking and intratracheal injection of lipopolysaccharide (LPS). The rats were randomly divided into eight groups: normal control, model control, three doses of herbs group, and three doses of herbs + itacitinib groups. The lung function indexes were measured by using a lung function tester, and changes in pathological features of all groups were observed by hematoxylin-eosin (HE) staining. The mRNA expression and protein expression levels in lung tissues were determined by real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical assay, respectively. Following treatment, IL-6 expression in lung tissues was significantly reduced compared with the model group. The results demonstrated that the medication was effective in alleviating the persistent airflow limitation and pathological features in COPD rats. Expression of JAK1/STAT3 in lung tissues was remarkably decreased. The JAK1/STAT3 pathway was inhibited, while SOCS3 expression was upregulated in the drug-treated groups compared with model control. However, after the addition of itacitinib (JAK1 inhibitor), the efficacy in each group was evidently impaired compared with herbs alone. Taken together, Zhuye Shigao Decoction combined with Qingqi Huatan Pills could improve the persistent airflow limitation and reduce lung inflammation and pathological changes of COPD possibly by regulating the expression of the IL-6-mediated JAK1/STAT3 pathway.
慢性阻塞性肺疾病(COPD)是一种病程较长的慢性疾病,常因呼吸道感染导致疾病急性加重。我们旨在探讨竹叶石膏汤联合清气化痰丸对慢性阻塞性肺疾病急性加重期(痰热壅肺型)大鼠白细胞介素(IL)-6介导的JAK1/STAT3信号通路的调节作用。通过烟熏和气管内注射脂多糖(LPS)建立肺痰热壅盛型慢性阻塞性肺疾病大鼠模型。将大鼠随机分为八组:正常对照组、模型对照组、中药三剂量组和中药三剂量+艾托替尼组。使用肺功能测试仪测量肺功能指标,通过苏木精-伊红(HE)染色观察各组病理特征变化。分别采用实时定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法和免疫组织化学法检测肺组织中mRNA表达和蛋白表达水平。治疗后,与模型组相比,肺组织中IL-6表达明显降低。结果表明,该药物可有效缓解慢性阻塞性肺疾病大鼠的持续性气流受限和病理特征。肺组织中JAK1/STAT3表达明显降低。与模型对照组相比,药物治疗组JAK1/STAT3信号通路受到抑制,而SOCS3表达上调。然而,加入艾托替尼(JAK1抑制剂)后,与单独使用中药相比,各组疗效明显受损。综上所述,竹叶石膏汤联合清气化痰丸可能通过调节IL-6介导的JAK1/STAT3信号通路的表达,改善慢性阻塞性肺疾病的持续性气流受限,减轻肺部炎症和病理变化。