MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan decoction therapy.

Abstract

Chronic obstructive pulmonary disease (COPD) features persistent inflammation and restricted airflow, with acute exacerbations of COPD (AECOPD) significantly worsening patient outcomes. This study aims to explore the role of Qingjin Huatan Decoction (QJHTT) on AECOPD with the syndrome of phlegm-heat obstruction of the lung. AECOPD was induced in male Sprague-Dawley rats using lipopolysaccharide and cigarette smoke exposure. Rats were treated with varying doses of QJHTT. miR-340-5p expression was quantified using qPCR. Lung histopathology was assessed with hematoxylin and eosin staining, and interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha were measured by enzyme-linked immunosorbent assay (ELISA). The effects on cell viability and apoptosis in primary airway epithelial cells were evaluated using Cell Counting Kit-8 and flow cytometry assays, respectively. The dual-luciferase reporter assay validated the interaction between miR-340-5p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2), and protein expression was analyzed by Western blot. QJHTT improved lung histopathology, reducing inflammatory cell infiltration, and alveolar damage. ELISA results showed reduced inflammatory cytokine levels in QJHTT-treated groups (P < 0.05). qPCR analysis demonstrated that QJHTT upregulated miR-340-5p expression (P < 0.05). miR-340-5p mimic enhanced cell viability and reduced apoptosis in primary airway epithelial cells (P < 0.05). Dual-luciferase reporter assay confirmed that miR-340-5p directly targets MAP3K2, leading to its downregulation (P < 0.05). QJHTT exerts therapeutic effects in phlegm-heat obstructing the lung type of AECOPD through upregulating miR-340-5p and inhibiting MAP3K2. This study highlights the QJHTT and miR-340-5p/MAP3K2 pathway for this disease treatment.