College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China.
Food Chem Toxicol. 2018 Jun;116(Pt B):59-69. doi: 10.1016/j.fct.2018.03.034. Epub 2018 Apr 7.
Lead (Pb) is one of the most relevant heavy metals contaminants which cause oxidative stress and threaten human health. The lung is one of the organs most severely damaged by Pb. In this study, we investigated the protective effect of grape seed procyanidin extract (GSPE) on Pb-induced lung injury in rats. We found that GSPE alleviated Pb-induced lung injury by relieving oxidative stress, reducing release of inflammatory factors, and inhibiting apoptosis. Furthermore, GSPE enhanced the antioxidant defense systems by activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway to promote downstream expression of heme oxygenase 1 and NAD(P)H quinone oxidoreductase 1. The subsequent ubiquitin-binding protein p62 (sequestosome 1), a downstream target of Nrf2, formed a positive feedback loop with Nrf2 during oxidative stress responses. GSPE treatment resulted in activation of adenosine monophosphate-activated protein kinase (AMPK), which was highly involved in Nrf2 activation. Overall, our findings demonstrate that theprotective effect of GSPE on Pb-induced lung injury arises from activation of the AMPK/Nrf2/p62 signaling pathway, thus providing a new approach for treatment of Pb intoxication.
铅（Pb）是一种最重要的重金属污染物之一，它会导致氧化应激，威胁人类健康。肺是受 Pb 损伤最严重的器官之一。在本研究中，我们研究了葡萄籽原花青素提取物（GSPE）对大鼠 Pb 诱导性肺损伤的保护作用。我们发现，GSPE 通过缓解氧化应激、减少炎症因子的释放和抑制细胞凋亡，减轻了 Pb 诱导的肺损伤。此外，GSPE 通过激活核因子-红细胞 2 相关因子（Nrf2）信号通路增强抗氧化防御系统，促进血红素加氧酶 1 和 NAD（P）H 醌氧化还原酶 1 的下游表达。随后，Nrf2 的下游靶蛋白 p62（自噬相关蛋白 62）在氧化应激反应中与 Nrf2 形成正反馈回路。GSPE 处理导致单磷酸腺苷激活蛋白激酶（AMPK）的激活，而 AMPK 高度参与 Nrf2 的激活。总的来说，我们的研究结果表明，GSPE 对 Pb 诱导性肺损伤的保护作用源于 AMPK/Nrf2/p62 信号通路的激活，从而为治疗 Pb 中毒提供了一种新的方法。
