目标:目前,对于肺缺血再灌注损伤(LIRI)尚无经证实有效的治疗方法。天然化合物为开发解决各种疾病的新药提供了有希望的前景。这项研究试图探索莱鲍迪甙B(RebB)作为LIRI治疗化合物的潜力,体内和体外。
方法:这项研究涉及利用人肺泡细胞系A549,由II型上皮细胞组成,进行氧-葡萄糖剥夺/恢复(OGD/R)以进行高通量体外细胞活力筛选。目的是鉴定最有希望的候选化合物。此外,采用体内大鼠肺缺血再灌注模型评估RebB的潜在保护作用。
结果:通过高通量筛选,RebB成为测试中最有前途的天然化合物。在A549OGD/R型号中,RebB表现出通过减轻凋亡来增强细胞活力的能力。在体内LIRI模型中,用RebB预处理显著减少凋亡细胞,血管周围水肿,和肺组织内的中性粒细胞浸润。此外,RebB主要通过升高IL-10水平同时降低IL-6、IL-8和TNF-α水平证明其减弱与LIRI相关的肺部炎症的能力。
结论:综合结果强烈表明RebB作为LIRI保护剂的潜力。这种作用归因于其对线粒体凋亡途径的抑制及其减轻炎症反应的能力。
OBJECTIVE: At present, no proven effective treatment is available for Lung Ischemiareperfusion Injury (LIRI). Natural compounds offer promising prospects for developing new drugs to address various diseases. This study sought to explore the potential of Rebaudioside B (Reb B) as a treatment compound for LIRI, both in vivo and in vitro.
METHODS: This study involved utilizing the human pulmonary alveolar cell line A549, consisting of epithelial type II cells, subjected to Oxygen-glucose Deprivation/recovery (OGD/R) for highthroughput in vitro cell viability screening. The aim was to identify the most promising candidate compounds. Additionally, an in vivo rat model of lung ischemia-reperfusion was employed to evaluate the potential protective effects of Reb B.
RESULTS: Through high-throughput screening, Reb B emerged as the most promising natural compound among those tested. In the A549 OGD/R models, Reb B exhibited a capacity to enhance cell viability by mitigating apoptosis. In the in vivo LIRI model, pre-treatment with Reb B notably decreased apoptotic cells, perivascular edema, and neutrophil infiltration within lung tissues. Furthermore, Reb B demonstrated its ability to attenuate lung inflammation associated with LIRI primarily by elevating IL-10 levels while reducing levels of IL-6, IL-8, and TNF-α.
CONCLUSIONS: The comprehensive outcomes strongly suggest Reb B\'s potential as a protective agent against LIRI. This effect is attributed to its inhibition of the mitochondrial apoptotic pathway and its ability to mitigate the inflammatory response.