Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Biomed Pharmacother. 2019 Mar;111:733-739. doi: 10.1016/j.biopha.2018.12.073. Epub 2019 Jan 3.
The disruption of the balance between antioxidants and oxidants plays a vital role in the pathogenesis of acute lung injury (ALI). Evidence has shown that Lycium barbarum polysaccharide (LBP) has antioxidant feature. We examined the efficacy and mechanisms of LBP on hyperoxia-induced acute lung injury (ALI) in the present study.
C57BL/6 wild-type (WT) mice and nuclear factor erythroid 2-related factor 2 (Nrf2)-deficient (Nrf2) mice were used in the present study. LBP was fed by gavages once daily for 1 week. Then, the mice were exposed to hyperoxia or room air for 72 h. Additional dosage of LBP was given per 24 h.
Reactive oxygen species production was increased in WT mice exposed to hyperoxia. Inflammatory cytokines including interleukin (IL)-1β as well as IL-6, and inflammatory cells were increased infiltration in the lung after 3 days hyperoxia exposure. Hyperoxia exposure also induced pulmonary edema and histopathological changes. These hyperoxia-induced changes were improved in LBP treated group. Moreover, elevated activities of heme oxygenase-1 and glutathione peroxidase and enhanced activation of Nrf2 were observed in mice treated with LBP. However, the benefit of LBP on hyperoxic ALI was abolished in Nrf2 mice. Moreover, our cell study showed that the LBP-induced activation of Nrf2 was dampened in pulmonary microvascular endothelial cells when the AMPK signal was inhibited by siRNA.
LBP improves hyperoxic ALI via Nrf2-dependent manner. The LBP-induced activation of Nrf2 is mediated, at least in part, by AMPK pathway.
抗氧化剂和氧化剂之间平衡的破坏在急性肺损伤（ALI）的发病机制中起着至关重要的作用。有证据表明，枸杞多糖（LBP）具有抗氧化作用。本研究旨在探讨 LBP 对高氧诱导的急性肺损伤（ALI）的疗效及其机制。
本研究使用 C57BL/6 野生型（WT）小鼠和核因子红细胞 2 相关因子 2（Nrf2）缺陷（Nrf2）小鼠。LBP 通过灌胃每天给药一次，持续 1 周。然后，将小鼠暴露于高氧或常氧中 72 小时。每 24 小时给予额外剂量的 LBP。
暴露于高氧的 WT 小鼠的活性氧（ROS）生成增加。在高氧暴露 3 天后，炎症细胞因子（包括白细胞介素（IL）-1β和 IL-6）和炎症细胞在肺部的浸润增加。高氧暴露还导致肺水肿和组织病理学改变。LBP 处理组改善了这些高氧诱导的变化。此外，在 LBP 处理的小鼠中观察到血红素加氧酶-1 和谷胱甘肽过氧化物酶的活性升高，以及 Nrf2 的激活增强。然而，在 Nrf2 小鼠中，LBP 对高氧性 ALI 的益处被消除。此外，我们的细胞研究表明，当 AMPK 信号被 siRNA 抑制时，LBP 诱导的 Nrf2 激活在肺微血管内皮细胞中被减弱。
LBP 通过 Nrf2 依赖的方式改善高氧性 ALI。LBP 诱导的 Nrf2 激活至少部分通过 AMPK 途径介导。
