Lianhua Qingke Preserves Mucociliary Clearance in Rat with Acute Exacerbation of Chronic Obstructive Pulmonary Disease by Maintaining Ciliated Cells Proportion and Protecting Structural Integrity and Beat Function of Cilia

Abstract

Xiaoqi Wang,1,2 Yuanjie Hao,3 Yujie Yin,4,5 Yunlong Hou,2,4,5 Ningxin Han,3 Yi Liu,3 Zhen Li,3 Yaru Wei,1 Kun Ma,1 Jiaojiao Gu,1 Yan Ma,1 Hui Qi,4,5 Zhenhua Jia1,4– 6 1Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China; 2Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang, 050035, People’s Republic of China; 3Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 4Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China; 5National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, People’s Republic of China; 6Department of Respiratory, Affiliated Yiling Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050091, People’s Republic of ChinaCorrespondence: Zhenhua Jia, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China, Email [email protected] Hui Qi, Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China, Email [email protected]: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD.Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 μg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and β-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera.Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF.Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.Keywords: goblet hyperplasia, ciliary density, ciliary length, ciliary ultrastructure, ciliary beat frequency, CBF

Keywords

• goblet hyperplasia
• ciliary density
• ciliary length
• ciliary ultrastructure
• ciliary beat frequency
• cbf.