As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

中文翻译：

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清肺通络合剂通过 mTOR 依赖性自噬减轻博来霉素诱导的大鼠肺部炎症和纤维化

特发性肺纤维化（IPF）作为一种以弥漫性肺泡炎和结构性肺泡疾病为特征的间质性纤维化疾病，其致死率较高，但治疗药物有限。据传，一种用于治疗病毒性肺炎的医院制剂清肺通络合剂（QFTL）对炎症和呼吸道疾病具有保护作用。本研究旨在证实其对博来霉素诱导的大鼠IPF是否具有治疗作用并阐明其作用机制。雄性 SD 大鼠随机分为以下组：对照组、模型组、CQ + QFTL（84 mg/kg 氯喹 (CQ) + 3.64 g/kg QFTL）、QFTL-L、M、H（3.64、7.28 和 14.56 g） /kg，分别）和吡非尼酮（PFD 420 mg/kg）。经过诱导建模和药物干预后，采集血样和肺组织进行进一步检测。检查体重和肺系数，结合苏木精和伊红（H&E）和Masson染色观察肺组织病变情况。采用酶联免疫吸附法（ELISA）和羟脯氨酸（HYP）测定试剂盒检测促炎因子（转化生长因子-β （ TGF- β）、肿瘤坏死因子-α（TNF- α）、白细胞介素）的变化。 -1 β (IL-1 β )) 和 HYP。采用免疫组织化学和蛋白质印迹法观察肺纤维化相关蛋白（α-平滑肌肌动蛋白（α -SMA）和基质金属蛋白酶12（MMP12））和自噬（P62和雷帕霉素机制靶点（mTOR））的变化。 QFTL治疗显着改善了博莱霉素对体重、肺系数和病理变化的不良影响。然后，QFTL 减少了博来霉素诱导的促炎介质和 HYP 的增加。 QFTL 减弱了肺纤维化和自噬标记蛋白的表达变化。此外，自噬抑制剂CQ显着逆转了HYP水平和α -SMA蛋白表达的下降趋势，而QFTL在BLM诱导的肺纤维化大鼠中得到了改善。总之，QFTL 可以通过 mTOR 依赖性自噬有效减轻博莱霉素诱导的大鼠炎症和肺纤维化。因此，QFTL有潜力成为临床实践中IPF的替代治疗方法。