School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
School of Basic Medicine, Chengdu University, Chengdu, 610106, China.
Chin J Integr Med. 2022 Dec;28(12):1081-1087. doi: 10.1007/s11655-021-3346-1. Epub 2021 Dec 7.
To investigate the effect of seabuckthorn berries extract (SBE) on pulmonary vascular hyperpermeability in the mice model of acute lung injury (ALI) induced by lipopolysaccharide (LPS).
Sixty Kunming mice were allocated into 6 groups by a random number table, including control, LPS, dexamethasone (Dex, 1 mg/kg), and 120, 240 and 480 mg/kg SBE groups, 10 mice in each group. Except the control group, mice were pre-treated with Dex and SBE, respectively, for 7 days before LPS was intraperitoneally injected to induce ALI. Pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in serum were measured using enzyme-linked immunosorbent assay. The expression of nuclear factor-kappa B (NF-κB) p65 in lung cells was determined by immunofluorescence analysis. The contents of cytoplasmic inhibitor of nuclear factor-κB kinase (IKK) and nuclear p65, as well as downstream proteins of E-selectin (CD62E) and intercellular adhesion molecule-1 (ICAM-1), were determined using Western blot analysis.
Histopathological observation confirmed SBE treatment alleviated morphological lesion induced by LPS. Compared with the LPS group, 480 mg/kg SBE significantly decreased the water content of lung, Evans blue accumulation in lung tissue, and protein concentration and neutrophils count in bronchoalveolar lavage fluid (P<0.01); moreover, 480 mg/kg SBE significantly suppressed release of TNF-α and IL-6, and down-regulated expressions of IKK, nuclear p65, ICAM-1 and CD62E (P<0.01).
SBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALI.
探讨沙棘果提取物（SBE）对脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠模型肺血管通透性的影响。
将 60 只昆明小鼠采用随机数字表法分为 6 组，每组 10 只，分别为对照组、LPS 组、地塞米松（Dex，1mg/kg）组、120、240 和 480mg/kg SBE 组。除对照组外，其余各组小鼠均预先用 Dex 和 SBE 处理 7 天，然后腹腔注射 LPS 建立 ALI 模型。通过组织病理学观察和跨血管渗漏测定评估肺血管通透性。采用酶联免疫吸附试验测定血清中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。免疫荧光分析检测肺细胞中核因子-κB（NF-κB）p65 的表达。Western blot 分析测定细胞质中核因子-κB 激酶（IKK）和核 p65 的含量以及 E-选择素（CD62E）和细胞间黏附分子-1（ICAM-1）的下游蛋白。
组织病理学观察证实 SBE 治疗可减轻 LPS 诱导的形态学损伤。与 LPS 组相比，480mg/kg SBE 可显著降低肺含水量、肺组织中 Evans 蓝蓄积、支气管肺泡灌洗液中蛋白浓度和中性粒细胞计数（P<0.01）；此外，480mg/kg SBE 还可显著抑制 TNF-α和 IL-6 的释放，并下调 IKK、核 p65、ICAM-1 和 CD62E 的表达（P<0.01）。
SBE 通过抑制 ALI 发病机制中的关键因素，在脂多糖刺激下维持了小鼠肺泡毛细血管屏障的完整性。
