Louqin Zhisou Decoction Inhibits Mucus Hypersecretion for Acute Exacerbation of Chronic Obstructive Pulmonary Disease Rats by Suppressing EGFR-PI3K-AKT Signaling Pathway and Restoring Th17/Treg Balance

Abstract

Airway mucus hypersecretion is the main pathogenic factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the control of mucus secretion is closely associated with survival. Louqin Zhisou decoction (LQZS) has been found to improve lung function and reduce sputum in AECOPD patients, but the mechanism remains unclear. This study aimed to explore the mechanism of LQZS against mucus hypersecretion in lung tissues of rat AECOPD model. Wistar rats were used to establish AECOPD model by intratracheal instillation of LPS in combination with the continuous cigarette smoking. Rats were administrated LQZS/clarithromycin (CAM)/distilled water via gavage every day and all rats were sacrificed after 30 days. BALF and lung tissues were obtained. Lung morphology, cytokines levels, MUC5AC mRNA transcription and protein expression, phosphorylation of the EGFR-PI3K-AKT signaling pathway, and molecules involved in Th17/Treg balance were evaluated. The results demonstrated that LQZS protected rats from decline in pulmonary function and ameliorated lung injury. LQZS treatment decreased the number of goblet cells in airway and suppressed MUC5AC mRNA and protein expression of lung tissues. Furthermore, LQZS attenuated the level of phospho-EGFR, phospho-PI3K and phospho-AKT in AECOPD rats. In addition, LQZS could inhibit the production of proinflammatory cytokines in BALF, including IL-6 and IL-17A and downregulate the secretion of NE and MCP-1, indicating that LQZS could limit inflammatory responses in AECOPD. Moreover, LQZS reversed RORγt and Foxp3 expression, the key transcription factors of Th17 and Treg, respectively. In conclusion, this research demonstrated the inhibitory effects of LQZS against mucus hypersecretion in AECOPD via suppressing EGFR-PI3K-AKT signaling pathway and restoring Th17/Treg balance.