目的 探讨益母草碱(Leo)通过腺苷酸活化蛋白激酶(AMPK)/ 沉默信息调节因子1(SIRT1)/核因子κB(NF-κB)信号通路改善急性呼吸窘迫综合征（ARDS）大鼠肺纤维化的作用机制。方法 通过气管滴注脂多糖的方式构建ARDS模型，48只模型大鼠随机分为ARDS组、Leo组、AMPK激活剂（AICAR）组、Leo+AMPK抑制剂化合物C（Comp C）组，每组12只，另取12只正常大鼠作为对照组。检测大鼠氧合指数、动脉血氧分压及肺湿干重比；HE、Masson染色分别检测肺组织病理、肺纤维化；Real-time PCR检测纤维化相关基因mRNA表达；ELISA检测炎症因子水平；Western blotting检测纤维化及AMPK/SIRT1/NF-κB通路蛋白表达。结果 与ARDS组比较，Leo组、AICAR组肺泡间隔变小，炎性细胞浸润现象有所改善，呈蓝染的胶原纤维沉积减少；氧合指数、动脉血氧分压、肺组织白细胞介素（IL）-10水平及封闭蛋白5（claudin-5）、p-AMPK、AMPK、SIRT1蛋白升高；肺湿干重比、肺组织Ⅰ型胶原蛋白（Col Ⅰ）、纤维连接蛋白（FN）、α平滑肌肌动蛋白（α-SMA）mRNA及蛋白表达降低，IL-6、肿瘤坏死因子α（TNF-α）水平及p-NF-κB p65/NF-κB p65比值降低（P<0.05）。Comp C减弱了益母草碱对ARDS大鼠肺纤维化的改善作用。结论 益母草碱可能通过激活AMPK/SIRT1抑制NF-κB通路改善ARDS大鼠肺纤维化。

Objective To investigate the mechanism by which leonurus(Leo) improves pulmonary fibrosis in rats with acute respiratory distress syndrome (ARDS) through the AMP-activated protein kinase (AMPK)/ sirtuin 1(SIRT1)/ nuclear factor-κB (NF-κB) pathway. Methods The ARDS model was established by intratracheal instillation of lipopolysaccharide. Forty-eight rats with successful model establishment were randomly divided into four groups, including the ARDS group, the Leo group, the AMPK activator (AICAR) group, and the Leo + AMPK inhibitor compound C (Comp C) group, with 12 rats in each group. Additionally, 12 normal rats were selected as the control(Ctrl) group. Oxygenation index, arterial partial oxygen pressure and lung wet-dry weight ratio were measured. HE and Masson staining were used to detect pulmonary tissue pathology and pulmonary fibrosis. Real-time PCR was used to detect the mRNA expression of pulmonary fibrosis-related genes. ELISA was employed to measure the levels of inflammatory factors, and Western blotting was applied to detect pulmonary fibrosis-related proteins and proteins in the AMPK/SIRT1/NF-κB pathway. Results Compared with the ARDS group, the Leo and the AICAR group exhibited thickened alveolar septa, reduced inflammatory cell infiltration, and decreased deposition of blue-stained collagen fibers. Oxygenation index, arterial partial pressure of oxygen, interleukin (IL)-10 levels, and claudin-5, p-AMPK, AMPK, and SIRT1 protein expression increased significantly. In contrast, lung wet/dry weight ratio, pulmonary mRNA and protein expressions of collagen type Ⅰ (ColⅠ), fibronectin (FN), and α-smooth muscle actin (α-SMA), levels of IL-6 and tumor necrosis factor α(TNF-α), and p-NF-κB p65/NF-κB p65 decreased markedly(P<0.05). Comp C attenuated the ameliorative effect of leonurus on pulmonary fibrosis in ARDS rats. Conclusion Leonurus may improve pulmonary fibrosis in ARDS rats by activating AMPK/SIRT1 to inhibit NF-κB pathway.