目的 評(píng)估丹參酮Ⅱ_A對(duì)急性呼吸衰竭（ARDS）大鼠模型的保護(hù)作用，并分析其通過(guò)核因子-κB(NF-κB)信號(hào)通路發(fā)揮抗炎、抗凋亡的分子機(jī)制。方法 采用脂多糖（LPS）誘導(dǎo)法建立ARDS大鼠模型。72只SPF級(jí)大鼠隨機(jī)分為對(duì)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(zhì)量比、肺組織病理評(píng)分、血清炎癥因子水平（TNF-α、IL-6、IL-1β）、肺泡灌洗液（BALF）細(xì)胞計(jì)數(shù)與分類(lèi)、肺組織中NF-κB信號(hào)通路相關(guān)蛋白表達(dá)[磷酸化核因子NF-κB抑制蛋白α(pIκBα)、p65、NF-κB DNA結(jié)合活性]、肺組織抗氧化指標(biāo)[超氧化物歧化酶（SOD）、丙二醛（MDA）]和肺組織細(xì)胞凋亡相關(guān)蛋白[B淋巴細(xì)胞瘤-2(Bcl-2)、Bcl-2相關(guān)X蛋白（Bax）、活化半胱氨酸蛋白酶-3(cleaved Caspase-3)]表達(dá)。結(jié)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(zhì)量比、病理評(píng)分、TNF-α、IL-6、IL-1β水平、BALF總細(xì)胞數(shù)和中性粒細(xì)胞比例、p-IκBα/IκBα、p65/β-actin、NF-κB DNA結(jié)合活性、MDA水平、Bax/Bcl-2值和cleaved Caspase-3表達(dá)均顯著降低（P<0.05、0.01），而SOD活性顯著升高（P<0.05）。結(jié)論 丹參酮Ⅱ_A通過(guò)調(diào)控NF-κB信號(hào)通路，能發(fā)揮抗炎、抗氧化和抗凋亡作用，對(duì)ARDS大鼠模型具有保護(hù)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(xiàng)目(2020559); 邢臺(tái)市重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(2023ZC136)