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This study aims to explore the therapeutic effect and mechanism of action of Zhisou Huatan Wan on rats with chronic obstructive pulmonary disease (COPD) of phlegm-heat obstructing the lungs. Animal experiments were approved by the Experimental Animal Ethics Committee of Henan University of Chinese Medicine (approval number: IACUC-202506002). Sixty male SD rats were randomly divided into six groups: control group, model group, erythromycin group (100 mg·kg-1), and low-dose (206.55 mg·kg-1), medium-dose (413.1 mg·kg-1), and high-dose Zhisou Huatan Wan (826.2 mg·kg-1) group. The rats were constructed with COPD of phlegm-heat obstructing the lungs by using smoke inhalation combined with intratracheal injection of lipopolysaccharide (LPS, 1 mg·kg-1) and cold air stimulation. The lung function, cough frequency, tracheal phenol red excretion, the degree of pulmonary tissue edema, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) of each group of rats were detected. H & E, Masson, and PAS staining were used to detect lung tissue lesions. The levels of apoptosis, oxidative stress and mitochondrial membrane potential in lung tissue, and peripheral blood immune cells (neutrophils, Treg cells, Th17 cells) were detected by flow cytometry. Transcriptomics analysis was used to screen core targets and signaling pathways. ELISA was applied to measure the levels of interleukin 17A (IL-17A), C-C chemokine ligand 7 (CCL7) and C-C motif chemokine ligand 20 (CCL20) in serum and lung tissue. qRT-PCR was used to detect the mRNA levels of IL-17A, CCL7 and CCL20 in lung tissue. IL-17A protein level was detected by Western blot. The results showed that Zhisou Huatan Wan significantly improved lung function, increased the level of blood oxygen partial pressure, mitochondrial membrane potential in lung tissue, and Treg cells in peripheral blood, promoted tracheal phenol red secretion, alleviated pathological lung injury, and reduced cough frequency, carbon dioxide partial pressure, the degree of pulmonary tissue edema, apoptosis and oxidative stress levels in lung tissue, as well as the levels of neutrophils and Th17 cells in peripheral blood. Zhisou Huatan Wan reduced the content of IL-17A, CCL7 and CCL20 in serum and lung tissue, and the corresponding mRNA levels in lung tissue, as well as the expression level of IL-17A in lung tissue. Transcriptomic analysis identified 78 differentially expressed genes, and primarily enriched in IL-17 signaling pathway, the chemokine signaling pathway and cytokine-cytokine receptor interaction. The results showed that Zhisou Huatan Wan had a significant improvement effect on COPD rats of phlegm-heat obstructing the lungs, and its mechanism may be related to the IL-17 signaling pathway.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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