Zhang Hailin, Chen Sha, Zeng Meichun, Lin Daopeng, Wang Yu, Wen Xunhang, Xu Changfu, Yang Li, Fan Xiaofang, Gong Yongsheng, Zhang Hongyu, Kong Xiaoxia
Department of Children's Respiration, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, China.
Cell Physiol Biochem. 2018;49(5):1918-1932. doi: 10.1159/000493653. Epub 2018 Sep 20.
BACKGROUND/AIMS: Acute lung injury (ALI) is induced by a variety of external and internal factors and leads to acute progressive respiratory failure. Previous studies have shown that apelin-13 can decrease the acute lung injury induced by LPS, but the specific mechanism is unclear. Therefore, a mouse lung injury model and a cell model were designed to explore the mechanism of how apelin-13 alleviates the acute lung injury caused by LPS.
The effect of apelin-13 on LPS-induced structural damage was determined by H&E staining and by the wet/dry weight ratio. The related inflammatory factors in BALF were examined by ELISA. The apoptotic pathway and the NF-κB and NLRP3 inflammasome pathways were evaluated by using Western blotting and immunofluorescence staining.
LPS induced the structural damage and the production of inflammatory cytokines in the lung tissues of mice. These deleterious effects were attenuated by apelin-13 administration. The protective effects of apelin-13 were associated with decreased reactive oxygen species (ROS) formation and the inhibition of the activation of the NF-κB and NLRP3 inflammasome pathways in mice and in Raw264.7 cells.
Taken together, these data suggest that apelin-13 administration ameliorates LPS-induced acute lung injury by suppressing ROS formation, as well as by inhibiting the NF-κB pathway and the activation of the NLRP3 inflammasome in the lungs.
背景/目的：急性肺损伤（ALI）由多种内外因素诱发，可导致急性进行性呼吸衰竭。既往研究表明，apelin-13可减轻脂多糖（LPS）诱导的急性肺损伤，但具体机制尚不清楚。因此，本研究设计了小鼠肺损伤模型和细胞模型，以探究apelin-13减轻LPS所致急性肺损伤的机制。
通过苏木精-伊红（H&E）染色及湿/干重比测定apelin-13对LPS诱导的结构损伤的影响。采用酶联免疫吸附测定（ELISA）法检测支气管肺泡灌洗液（BALF）中相关炎症因子。运用蛋白质免疫印迹法和免疫荧光染色法评估凋亡途径以及核因子κB（NF-κB）和NLRP3炎性小体途径。
LPS诱导小鼠肺组织出现结构损伤并产生炎性细胞因子。给予apelin-13可减轻这些有害作用。apelin-13的保护作用与小鼠及Raw264.7细胞中活性氧（ROS）生成减少以及NF-κB和NLRP3炎性小体途径激活受到抑制有关。
综上所述，这些数据表明，给予apelin-13可通过抑制ROS生成以及抑制肺组织中的NF-κB途径和NLRP3炎性小体激活来改善LPS诱导的急性肺损伤。
