Gao Qi, Chang Ningqing, Liu Donglian
Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.
J Int Med Res. 2021 Feb;49(2):300060520986351. doi: 10.1177/0300060520986351.
To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI).
Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.
Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI and . In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both and . Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed and following sufentanil treatment. miR-129-5p targeted the 3' untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells.
Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.
探讨舒芬太尼对急性肺损伤（ALI）保护作用的潜在机制。
通过气管内滴注给予大鼠脂多糖（LPS）以建立ALI模型。用LPS刺激BEAS-2B细胞。使用荧光素酶报告基因检测法评估IκB的靶点和启动子活性。通过末端脱氧核苷酸转移酶dUTP缺口末端标记法评估BEAS-2B细胞的凋亡。
舒芬太尼治疗显著减轻了肺组织的病理变化、肺水肿以及与ALI相关的炎症因子分泌。此外，舒芬太尼抑制了LPS诱导的细胞凋亡并激活了NF-κB。而且，舒芬太尼治疗后观察到高迁移率族蛋白B1（HMGB1）蛋白水平上调和miR-129-5p水平下调。miR-129-5p靶向3'非翻译区，其抑制作用降低了IκB-α的启动子活性。抑制miR-129-5p显著削弱了舒芬太尼对LPS处理的BEAS-2B细胞的保护作用。
舒芬太尼通过调节miR-129-5p/HMGB1轴增强IκB-α表达，表明舒芬太尼是一种用于ALI保护的候选药物，并为临床治疗提供了途径。
