目的 基于自噬对环磷酸鸟苷-磷酸腺苷合酶（cyclic GMP-AMP synthase，cGAS）/干扰素基因刺激蛋白（stimulator of interferon genes，STING）通路的影响，探讨清咳平喘颗粒治疗慢性阻塞性肺疾病急性加重（acute exacerbation of chronic obstructive pulmonary disease，AECOPD）模型大鼠的作用机制。方法 雄性SD大鼠随机分为对照组、模型组、地塞米松（4 mg/kg）组及清咳平喘颗粒低、高剂量（2.5、5.0 g/kg）组和自噬激活剂雷帕霉素（1 mg/kg）组，每组10只。采用香烟烟雾暴露联合脂多糖（lipopolysaccharides，LPS）气道滴注法建立AECOPD大鼠模型，给予药物干预后，观察各组大鼠一般状态；检测大鼠肺功能与肺组织病理变化；分析外周血和肺泡灌洗液（bronchoalveolar lavage fluid，BALF）中炎性细胞数量；ELISA法测定BALF中白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和IL-1β水平；qRT-PCR检测肺组织β干扰素（interferon-β，IFN-β）和趋化因子C-X-C基序配体10（chemokine C-X-C motif ligand 10，CXCL10）mRNA表达；Western blotting检测肺组织cGAS、STING、p-STING、TANK结合激酶1（TANK binding kinase 1，TBK1）、p-TBK1、核因子-κB p65（nuclear factor-κB p65，NF-κB p65）、p-NF-κB p65、微管相关蛋白轻链3（microtubule-associated protein light chain 3，LC3）和自噬相关基因5（autophagy-related gene 5，ATG5）的蛋白表达。结果 与模型组比较，各给药组大鼠肺组织病理损伤和肺功能均有改善（P＜0.01、0.001），外周血和BALF中炎性细胞数量显著降低（P＜0.05、0.01、0.001），BALF中炎症因子水平显著降低（P＜0.05、0.01、0.001）；清咳平喘颗粒高剂量组和雷帕霉素组大鼠肺组织IFN-β、CXCL10 mRNA表达水平显著降低（P＜0.01、0.001），cGAS、p-STING、p-TBK1、p-NF-κB p65蛋白表达水平显著降低（P＜0.05、0.01、0.001），LC3-II/I和ATG5蛋白表达水平显著升高（P＜0.01、0.001）。结论 清咳平喘颗粒通过激活自噬抑制cGAS/STING通路，从而减轻AECOPD持续炎症反应。

Objective To investigate the mechanism of Qingke Pingchuan Granules (清咳平喘颗粒) in the treatment of rats with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) based on the effect of autophagy on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. Methods Male SD rats were randomly divided into control group, model group, dexamethasone (4 mg/kg) group, Qingke Pingchuan Granules low-, high-dose (2.5, 5.0 g/kg) groups and autophagy activator rapamycin (1 mg/kg) group, with 10 rats in each group. An AECOPD rat model was established using cigarette smoke exposure combined with lipopolysaccharide (LPS) airway instillation. After drug intervention, the general status of rats in each group was observed. The pulmonary function and pathological changes in lung tissue were detected. The numbers of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF) were analyzed. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β in BALF were measured by ELISA. The mRNA expressions of interferon-β (IFN-β) and chemokine C-X-C motif ligand 10 (CXCL10) in lung tissue were detected by qRT-PCR. The protein expressions of cGAS, STING, p-STING, TANK binding kinase 1 (TBK1), p-TBK1, nuclear factor-κB p65 (NF-κB p65), p-NF-κB p65, microtubule-associated protein light chain 3 (LC3) and autophagy-related gene 5 (ATG5) in lung tissue were determined by Western blotting. Results Compared with model group, the pathological damage and lung function of rats in each treatment group were improved (P < 0.01, 0.001), the numbers of inflammatory cells in peripheral blood and BALF were significantly reduced (P < 0.05, 0.01, 0.001), and the levels of inflammatory factors in BALF were significantly reduced (P < 0.05, 0.01, 0.001). The mRNA expression levels of IFN-β and CXCL10 in lung tissue of rats in Qingke Pingchuan Granules high-dose group and rapamycin group were significantly reduced (P < 0.01, 0.001), the protein expression levels of cGAS, p-STING, p-TBK1 and p-NF-κB p65 were significantly reduced (P < 0.05, 0.01, 0.001), the protein expression levels of LC3-II/I and ATG5 were significantly increased (P < 0.01, 0.001). Conclusion Qingke Pingchuan Granules inhibit cGAS/STING pathway by activating autophagy, thereby alleviating the persistent inflammatory response of AECOPD.

R285.5

河北省中医药管理局科研计划项目（2021079）；河北省中医药管理局科研计划项目（2019029）