目的 评估丹参酮Ⅱ_A对急性呼吸衰竭（ARDS）大鼠模型的保护作用，并分析其通过核因子-κB(NF-κB)信号通路发挥抗炎、抗凋亡的分子机制。方法 采用脂多糖（LPS）诱导法建立ARDS大鼠模型。72只SPF级大鼠随机分为对照组、模型组、地塞米松组以及丹参酮Ⅱ_A低、中、高剂量（5、10、20 mg/kg）组，每组各12只。比较各组大鼠肺组织湿/干质量比、肺组织病理评分、血清炎症因子水平（TNF-α、IL-6、IL-1β）、肺泡灌洗液（BALF）细胞计数与分类、肺组织中NF-κB信号通路相关蛋白表达[磷酸化核因子NF-κB抑制蛋白α(pIκBα)、p65、NF-κB DNA结合活性]、肺组织抗氧化指标[超氧化物歧化酶（SOD）、丙二醛（MDA）]和肺组织细胞凋亡相关蛋白[B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白（Bax）、活化半胱氨酸蛋白酶-3(cleaved Caspase-3)]表达。结果 与模型组相比，地塞米松组和丹参酮Ⅱ_A各剂量组肺组织湿/干质量比、病理评分、TNF-α、IL-6、IL-1β水平、BALF总细胞数和中性粒细胞比例、p-IκBα/IκBα、p65/β-actin、NF-κB DNA结合活性、MDA水平、Bax/Bcl-2值和cleaved Caspase-3表达均显著降低（P<0.05、0.01），而SOD活性显著升高（P<0.05）。结论 丹参酮Ⅱ_A通过调控NF-κB信号通路，能发挥抗炎、抗氧化和抗凋亡作用，对ARDS大鼠模型具有保护效果。

Objective To evaluate the protective effect of tanshinone Ⅱ_A on acute respiratory failure（ARDS） rat model and analyze the molecular mechanism of its protective effect through the NF-κB signaling pathway. Methods An ARDS rat model was established using lipopolysaccharide（LPS） induction. 72 SPF grade animals were randomly divided into control group, model group, dexamethasone group, and low, medium, and high（5, 10, and 20 mg/kg） dose groups of tanshinone Ⅱ_A, with 12 rats in each group. The evaluation indicators include lung tissue wet/dry weight ratio, lung tissue pathological score, serum inflammatory factor levels（TNF-α, IL-6, IL-1β）, bronchoalveolar lavage fluid（BALF） cell count and classification, expression of NF-κB signaling pathway related proteins（p-IκBα, p65,NF-κB DNA binding activity）, lung tissue antioxidant indicators（SOD, MDA）, and lung tissue cell apoptosis related proteins（Bax Bcl-2, cleaved Caspase-3）. Results Compared with the model group, wet/dry weight ratio of lung tissue, pathological score, TNF-α, IL-6, IL-1β, the total cell count and neutrophil ratio, p-IκBα/IκBα, p65/β-actin, NF-κB DNA binding activity, MDA, Bax/Bcl-2, and the expression of cleaved Caspase-3 in the dexamethasone group and the low, medium, and high dose groups of tanshinone Ⅱ_A were decreased significantly（P＜0.05, 0.01）, while SOD activity was increased significantly（P＜0.05）. Conclusion Tanshinone Ⅱ_A exerts significant anti-inflammatory, antioxidant, and anti-apoptotic effects by regulating the NF-κB signaling pathway, and has a significant protective effect on ARDS rat models.

R285.5

河北省中医药管理局项目(2020559); 邢台市重点研发计划项目(2023ZC136)