Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
Lung. 2020 Apr;198(2):323-331. doi: 10.1007/s00408-020-00321-w. Epub 2020 Jan 20.
Obstructive sleep apnea (OSA) is associated with lung injury. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis. The present study aims to evaluate the effect of resveratrol (Res) on CIH-induced lung apoptosis and inflammation in a rat model of CIH.
Rats were randomly allocated to normoxia (control), CIH, and CIH + Res groups (n = 10 in each group). The CIH exposure duration was 12 weeks. Rats in the CIH + Res group were additionally administered Res (50 mg kg d). Inflammatory cytokine levels were detected by enzyme-linked immunosorbent assays (ELISAs). A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was conducted to evaluate the apoptosis rate. Bax, cleaved caspase-3, Nrf2 and HO-1 protein levels were detected by western blotting.
The IL-6 and TNF-α levels in the serum and alveolar lavage fluid in the CIH group were markedly higher than those in the control group. The percentage of apoptotic cells in the CIH group was higher than that in the control group. Bax and cleaved caspase-3 protein levels were increased in the CIH group compared with those in the control group. Nrf2 and HO-1 protein levels were decreased in the CIH group compared with those in the control group (p < 0.05). Compared with the CIH group, rats in the CIH + Res group had lower percentages of apoptotic cells, lower IL-6, TNF-α, Bax and cleaved caspase-3 protein levels, and higher Nrf2 and HO-1 protein levels (p < 0.05).
Res attenuates CIH-related inflammatory reactions and apoptosis in lung tissue by activating the Nrf2/ARE pathway.
阻塞性睡眠呼吸暂停（OSA）与肺损伤有关。作为 OSA 的一种新的病理生理学标志，慢性间歇性低氧（CIH）增强细胞凋亡。本研究旨在评估白藜芦醇（Res）对 CIH 诱导的大鼠模型中肺细胞凋亡和炎症的影响。
将大鼠随机分配到常氧（对照）、CIH 和 CIH+Res 组（每组 10 只）。CIH 暴露时间为 12 周。CIH+Res 组大鼠另外给予 Res（50mg/kg/d）。通过酶联免疫吸附测定（ELISA）检测炎症细胞因子水平。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）测定评估细胞凋亡率。通过蛋白质印迹法检测 Bax、裂解的 caspase-3、Nrf2 和 HO-1 蛋白水平。
CIH 组血清和肺泡灌洗液中的白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）水平明显高于对照组。CIH 组的细胞凋亡率高于对照组。与对照组相比，CIH 组 Bax 和裂解的 caspase-3 蛋白水平升高。与对照组相比，CIH 组 Nrf2 和 HO-1 蛋白水平降低（p<0.05）。与 CIH 组相比，CIH+Res 组的细胞凋亡率较低，IL-6、TNF-α、Bax 和裂解的 caspase-3 蛋白水平较低，Nrf2 和 HO-1 蛋白水平较高（p<0.05）。
Res 通过激活 Nrf2/ARE 通路减轻 CIH 相关的肺部炎症反应和细胞凋亡。
