Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1
Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1
复制标题
蛇床子素通过上调 Nrf-2/硫氧还蛋白 1 改善小鼠急性肺损伤
DOI：
10.1016/j.resp.2013.04.014
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发表时间：
2013-08-15
影响因子：
2.3
通讯作者：
Li, Zhi-Chao
中科院分区：
文献类型：
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作者：
Chen, Xiang-Jun;Zhang, Bo;Li, Zhi-Chao
抑制活性氧（ROS）已被视为治疗急性肺损伤（ALI）的治疗靶点。蛇床子素是中草药中的一种有效成分，因其具有抗炎、抗氧化等多种药理作用而受到越来越多的关注。本研究旨在探讨蛇床子素对脂多糖（LPS）诱导的ALI的作用。采用实时荧光定量PCR （real-time PCR）、反转录PCR （RT-PCR）和Western blot检测细胞中硫氧还蛋白1 （Trx1）和核因子红细胞2相关因子2 （Nrf2）的mRNA和蛋白表达水平。流式细胞术检测ROS的产生。我们的研究结果显示，与未处理的LPS组相比，蛇床子素处理提高了中、高剂量组小鼠的存活率。此外，蛇蛇素治疗可显著改善lps诱导的肺病理损伤，降低肺损伤评分、肺干湿比和支气管肺泡灌洗液（BALF）总蛋白水平。蛇床子素显著降低大鼠肺匀浆中H2O2、MDA和(OH)- o中心点水平。在体外，蛇床子素+ LPS组LDH和ROS明显降低。此外，蛇床子素在体内和体外均能提高Nrf2和Trx1 mRNA和蛋白的表达。Nrf2 siRNA （siNrf2）可抑制蛇蛇素对ALI的有益作用。综上所述，本研究表明蛇尾素通过上调Nrf-2/Trx-1通路对lps诱导的ALI具有保护作用。(C) 2013 Elsevier B.V.版权所有
Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and (OH)-O-center dot levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole + LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway. (C) 2013 Elsevier B.V. All rights reserved.