目的 探究人参皂苷Rg₁对大鼠肺纤维化（pulmonary fibrosis，PF）的影响及作用机制。方法 50只雄性SD大鼠随机分为对照组、模型组、人参皂苷Rg₁（72 mg/kg）组、腺苷酸活化蛋白激酶（adenosine monophosphate activated protein kinase，AMPK）激动剂（200 mg/kg）组、人参皂苷Rg₁（72 mg/kg）＋AMPK抑制剂（20 mg/kg）组，每组10只。除对照组外，其余各组大鼠气管内注射博来霉素（5 mg/kg）构建大鼠PF模型。造模成功后2 d开始给药，连续给药28 d后检测大鼠肺功能指标；采用苏木素-伊红（HE）、Masson染色观察肺组织病理变化；采用免疫组化检测肺组织I型胶原（collagen I）和α-肌动球蛋白（α-smooth muscle actin，α-SMA）表达；采用试剂盒测定肺组织羟脯氨酸（hydroxyproline，Hyp）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、IL-1β和IL-18水平；采用Western blotting检测肺组织p-AMPK/AMPK、NOD样蛋白3（NOD-like receptor protein 3，NLRP3）、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）、消皮素D（gasdermin D，GSDMD）、IL-1β和IL-18蛋白表达。结果 与模型组比较，人参皂苷Rg₁和AMPK激动剂组大鼠肺功能指标明显升高（P＜0.05），肺纤维化程度改善，肺指数及肺组织Hyp、TNF-α、IL-6、IL-1β和IL-18水平均明显降低（P＜0.05），肺组织collagen I、α-SMA、NLRP3、cleaved Caspase-1/pro Caspase-1、GSDMD-N/ GSDMD、IL-1β和IL-18蛋白表达水平均显著降低（P＜0.05），p-AMPK/AMPK蛋白表达升高（P＜0.05）。与人参皂苷Rg₁组比较，人参皂苷Rg₁＋AMPK抑制剂组大鼠肺功能指标降低（P＜0.05），肺纤维化程度加重，肺指数及肺组织Hyp、TNF-α、IL-6、IL-1β和IL-18水平均明显增加（P＜0.05），肺组织collagen I、α-SMA、NLRP3、cleaved Caspase-1/pro Caspase-1、GSDMD-N/GSDMD、IL-1β和IL-18蛋白表达升高（（P＜0.05），p-AMPK/AMPK表达降低（P＜0.05）。结论 人参皂苷Rg₁能够抑制AMPK/NLRP3介导的细胞焦亡改善博来霉素诱导的大鼠PF。

Objective To investigate the effect and mechanism of ginsenoside Rg₁ on pulmonary fibrosis (PF) in rats. Methods A total of 50 male SD rats were randomly divided into control group, model group, ginsenoside Rg₁ (72 mg/kg) group, adenosine monophosphate activated protein kinase (AMPK) agonist (200 mg/kg) group and ginsenoside Rg₁ (72 mg/kg) + AMPK inhibitor group (20 mg/kg), with 10 rats in each group. Except for the control group, rats in the other groups were injected with bleomycin (5 mg/kg) into trachea to establish a rat model of PF. The drug was administered two days after successful modeling. After continuous administration for 28 d, pulmonary function indexes of rats were detected; HE and Masson staining were used to observe pathological changes of lung tissue; Immunohistochemistry was used to detect the expressions of collagen I and α-smooth muscle actin (α-SMA) in lung tissue; Levels of hydroxyproline (Hyp), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-18 in lung tissue were measured by kit. p-AMPK/AMPK, NOD-like receptor protein 3 (NLRP3), cysteine-aspartate protease-1 (Caspase-1), gasdermin D (GSDMD), IL-1β and IL-18 protein expressions in lung tissue were detected by Western blotting. Results Compared with model group, lung function indexes of rats in ginsenoside Rg₁ group and AMPK agonist group were significantly increased (P < 0.05), degree of pulmonary fibrosis was improved, lung index and levels of Hyp, TNF-α, IL-6, IL-1β and IL-18 in lung tissue were significantly decreased (P < 0.05), collagen I, α-SMA, NLRP3, cleaved Caspase-1/pro Caspase-1, GSDMD-N/GSDMD, IL-1β and IL-18 protein expressions in lung tissues were significantly decreased (P < 0.05), while p-AMPK/AMPK protein expression was increased (P < 0.05). Compared with ginsenoside Rg₁ group, lung function index in ginsenoside Rg₁ + AMPK inhibitor group was decreased (P < 0.05), pulmonary fibrosis was aggravated, lung index and levels of Hyp, TNF-α, IL-6, IL-1β and IL-18 in lung tissue were significantly increased (P < 0.05), collagen I, α-SMA, NLRP3, cleansed caspase-1/pro caspase-1, GSDMD-N/GSDMD, IL-1β and IL-18 protein expressions in lung tissue were increased (P < 0.05), but p-AMPK/AMPK expression was decreased (P < 0.05). Conclusion Ginsenoside Rg₁ can inhibit AMPK/NLRP3-mediated cell scorch and improve bleomycin-induced PF in rats.

R285.5

河南省高等学校自然科学重点科研项目（21B320122）