目的 評估丹參酮Ⅱ_A對急性呼吸衰竭（ARDS）大鼠模型的保護作用，并分析其通過核因子-κB(NF-κB)信號通路發(fā)揮抗炎、抗凋亡的分子機制。方法 采用脂多糖（LPS）誘導法建立ARDS大鼠模型。72只SPF級大鼠隨機分為對照組、模型組、地塞米松組以及丹參酮Ⅱ_A低、中、高劑量（5、10、20 mg/kg）組，每組各12只。比較各組大鼠肺組織濕/干質量比、肺組織病理評分、血清炎癥因子水平（TNF-α、IL-6、IL-1β）、肺泡灌洗液（BALF）細胞計數(shù)與分類、肺組織中NF-κB信號通路相關蛋白表達[磷酸化核因子NF-κB抑制蛋白α(pIκBα)、p65、NF-κB DNA結合活性]、肺組織抗氧化指標[超氧化物歧化酶（SOD）、丙二醛（MDA）]和肺組織細胞凋亡相關蛋白[B淋巴細胞瘤-2(Bcl-2)、Bcl-2相關X蛋白（Bax）、活化半胱氨酸蛋白酶-3(cleaved Caspase-3)]表達。結果 與模型組相比，地塞米松組和丹參酮Ⅱ_A各劑量組肺組織濕/干質量比、病理評分、TNF-α、IL-6、IL-1β水平、BALF總細胞數(shù)和中性粒細胞比例、p-IκBα/IκBα、p65/β-actin、NF-κB DNA結合活性、MDA水平、Bax/Bcl-2值和cleaved Caspase-3表達均顯著降低（P<0.05、0.01），而SOD活性顯著升高（P<0.05）。結論 丹參酮Ⅱ_A通過調控NF-κB信號通路，能發(fā)揮抗炎、抗氧化和抗凋亡作用，對ARDS大鼠模型具有保護效果。

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

河北省中醫(yī)藥管理局項目(2020559); 邢臺市重點研發(fā)計劃項目(2023ZC136)