目的 探讨神香草提取物对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）大鼠气道炎症及黏液高分泌的影响，并分析其潜在作用机制。方法 雄性SD大鼠随机分为对照组、模型组、氨溴索（6.3 mg/kg）组、鲜竹沥（6.3 mL/kg）及神香草提取物低、中、高剂量（35、70、140 mg/kg）组，每组10只。除对照组外，其余各组均采用香烟烟雾暴露联合气道内脂多糖（lipopolysaccharide，LPS）注入法建立COPD模型，连续给药18 d。观察大鼠一般状态，检测每分钟通气量（minute volume，MV）、吸气峰流速（peak inspiratory，flow，PIF）、呼气峰流速（peak expiratory flow，PEF）和呼气中期流速（expiratory flow-50，EF50）；分别测定外周血和肺泡灌洗液（bronchial alveolar lavage fluid，BALF）中炎性细胞数量；ELISA法检测肺组织中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）、趋化因子C-X-C基序配体1（chemokine C-X-C motif ligand 1，CXCL1）、黏蛋白5AC（mucin 5AC，MUC5AC）水平；qRT-PCR和Western blotting检测肺组织表皮生长因子受体（epidermal growth factor receptor，EGFR）/磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）通路相关基因及蛋白表达；免疫组化法检测肺组织中MUC5AC表达。结果 与模型组比较，神香草提取物组大鼠一般状态改善，体质量显著升高（P＜0.05），肺功能指标显著升高（P＜0.05、0.01、0.001），外周血和BALF中白细胞、中性粒细胞和巨噬细胞数量显著降低（P＜0.05、0.01、0.001），肺组织中TNF-α水平显著降低（P＜0.01），肺组织病理损伤减轻，炎症浸润、胶原沉积及黏液分泌减少，肺组织中EGFR/PI3K通路及黏蛋白1（mucin 1，MUC1）、MUC5AC的mRNA和蛋白表达水平均显著降低（P＜0.05、0.01、0.001）。结论 神香草提取物可有效缓解COPD大鼠气道炎症，抑制气道黏液高分泌，改善肺功能，其作用机制可能与抑制EGFR/PI3K信号通路相关。

Objective To investigate the effect of Hyssopus cuspidatus extract on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease (COPD) and explore its potential mechanism. Methods Male SD rats were randomly divided into control group, model group, ambroxol (6.3 mg/kg) group, succus bambusae (6.3 mL/kg) group and H. cuspidatus extract low-, medium- and high-dose (35, 70, 140 mg/kg) groups, with 10 rats in each group. Except for the control group, COPD model was established by cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide, after continuous administration for 18 d, the general state of rats was observed, minute volume (MV), peak inspiratory flow (PIF), peak expiratory flow (PEF) and expiratory flow-50 (EF50) were measured. The numbers of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF) were determined respectively. ELISA method was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), chemokine C-X-C motif ligand 1 (CXCL1) and mucin 5AC (MUC5AC) in lung tissue. qRT-PCR and Western blotting were used to detect the expressions of genes and proteins related to the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K) pathway in lung tissue. Immunohistochemistry was used to detect the expression of MUC5AC in lung tissue. Results Compared with model group, the general condition of rats in H. cuspidatus extract group was improved, body weight was significantly increased (P < 0.05), lung function indicators were significantly increased (P < 0.05, 0.01, 0.001), the numbers of white blood cells, neutrophils and macrophages in peripheral blood and BALF were significantly decreased (P < 0.05, 0.01, 0.001), TNF-α level in lung tissue was significantly decreased (P < 0.01), pathological damage in lung tissue was reduced, inflammation infiltration, collagen deposition and mucus secretion were decreased, the mRNA and protein expression levels of EGFR/PI3K pathway, mucin 1 (MUC1) and MUC5AC in lung tissue were significantly reduced (P < 0.05, 0.01, 0.001). Conclusion H. cuspidatus extract could effectively alleviate airway inflammation in COPD rats, inhibit airway mucus hypersecretion, and improve lung function. Its mechanism may be related to the inhibition of EGFR/PI3K signaling pathway.

R285.5

新疆维吾尔自治区自然科学基金青年基金项目（2022D01B189）；新疆维吾尔自治区重点研发计划项目（2024B02023）；新疆维吾尔自治区药学会科研基金项目（YXH202401）