Division of Pathogenic Biology, Department of Laboratory Medicine, Shaoyang University, Shaoyang, PR China.
Department of Basic Medicine, Xiangnan University, Chenzhou, PR China.
Int Immunopharmacol. 2018 Jul;60:18-25. doi: 10.1016/j.intimp.2018.04.032. Epub 2018 Apr 24.
The present study is to investigate the protective effect of cordycepin on inflammatory reactions in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), as well as the underlying mechanism.
Wistar rat model of ALI was induced by intravenous injection of LPS (30 mg/kg body weight). One hour later, intravenous injection of cordycepin (1, 10 or 30 mg/kg body weight) was administered. The wet-to-dry weight ratio of lung tissues and myeloperoxidase activity in the lung tissues were measured. The contents of nitrite and nitrate were measured by reduction method, while chemiluminescence was used to determine the content of superoxide. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of mRNA and protein, respectively. Colorimetry was performed to determine the enzymatic activity of heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 was identified by Western blotting. The plasma contents of cytokines were measured by enzyme-linked immunosorbent assay.
Cordycepin enhanced the expression and enzymatic activity of HO-1 in ALI rats, and activated Nrf2 by inducing the translocation of Nrf2 from cytoplasm to nucleus. In addition, cordycepin regulated the secretion of TNF-α, IL-6 and IL-10 via HO-1, and suppressed inflammation in lung tissues of ALI rats by inducing the expression of HO-1. HO-1 played important roles in the down-regulation of superoxide levels in lung tissues by cordycepin, and HO-1 expression induced by cordycepin affected nitrite and nitrate concentrations in plasma and iNOS protein expression in lung tissues. Cordycepin showed protective effect on injuries in lung tissues.
The present study demonstrates that cordycepin alleviates inflammation induced by LPS via the activation of Nrf2 and up-regulation of HO-1 expression.
本研究旨在探讨虫草素对脂多糖（LPS）诱导的急性肺损伤（ALI）大鼠炎症反应的保护作用及其机制。
采用静脉注射 LPS（30mg/kg 体重）诱导 Wistar 大鼠 ALI 模型。1 小时后，静脉注射虫草素（1、10 或 30mg/kg 体重）。测量肺组织湿重/干重比和肺组织髓过氧化物酶活性。采用还原法测定亚硝酸盐和硝酸盐含量，化学发光法测定超氧阴离子含量。实时定量聚合酶链反应和 Western blot 分别用于测定 mRNA 和蛋白的表达。比色法测定血红素加氧酶-1（HO-1）的酶活性。Western blot 鉴定 Nrf2 的核转位。酶联免疫吸附试验测定细胞因子的血浆含量。
虫草素增强了 ALI 大鼠 HO-1 的表达和酶活性，并通过诱导 Nrf2 从细胞质向核内转位激活了 Nrf2。此外，虫草素通过 HO-1 调节 TNF-α、IL-6 和 IL-10 的分泌，并通过诱导 HO-1 的表达抑制 ALI 大鼠肺组织的炎症。HO-1 在虫草素下调肺组织中超氧水平中起重要作用，虫草素诱导的 HO-1 表达影响血浆中硝酸盐和亚硝酸盐浓度以及肺组织中 iNOS 蛋白的表达。虫草素对肺组织损伤具有保护作用。
本研究表明，虫草素通过激活 Nrf2 和上调 HO-1 表达缓解 LPS 诱导的炎症。
