Zhang Liang, Wang Shuxian, Zhang Ying, Li Fenghuan, Yu Chaoxiao
Department of Respiratory and Critical Care Medicine, Yantaishan Hospital, Yantai, Shandong 264001, P.R. China.
Department of Respiratory, Yantai Beihai Hospital, Yantai, Shandong 265701, P.R. China.
Exp Ther Med. 2023 Apr 20;25(6):265. doi: 10.3892/etm.2023.11964. eCollection 2023 Jun.
Oxidative stress and inflammation are both involved in the pathogenesis of lung ischemia-reperfusion (I/R) injury. Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant properties. The present study hypothesized that SFN may protect against lung I/R injury via the regulation of antioxidant and anti-inflammatory-related pathways. A rat model of lung I/R injury was established, and rats were randomly divided into 3 groups: Sham group, I/R group, and SFN group. It was shown that SFN protected against a pathological inflammatory response via inhibition of neutrophil accumulation and in the reduction of the serum levels of the pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α. SFN treatment also significantly inhibited lung reactive oxygen species production, decreased the levels of 8-OH-dG and malondialdehyde, and reversed the decrease in the antioxidant activities of the enzymes catalase, superoxide dismutase, and glutathione peroxidase in the lungs of the I/R treated rats. In addition, SFN ameliorated I/R-induced lung apoptosis in rats by suppressing Bax and cleaved caspase-3 levels and increased Bcl-2 expression. Furthermore, SFN treatment activated an Nrf2-related antioxidant pathway, as indicated by the increased nuclear transfer of Nrf2 and the downstream HO-1 and NADPH quinone oxidoreductase-1. In conclusion, these findings suggested that SFN protected against I/R-induced lung lesions in rats via activation of the Nrf2/HO-1 pathway and the accompanied anti-inflammatory and anti-apoptotic effects.
氧化应激和炎症均参与肺缺血再灌注(I/R)损伤的发病机制。萝卜硫素(SFN)是一种具有细胞保护、抗炎和抗氧化特性的天然产物。本研究假设,SFN可能通过调节抗氧化和抗炎相关途径来预防肺I/R损伤。建立了大鼠肺I/R损伤模型,并将大鼠随机分为3组:假手术组、I/R组和SFN组。结果表明,SFN通过抑制中性粒细胞聚集以及降低促炎细胞因子IL-6、IL-1β和TNF-α的血清水平,预防病理性炎症反应。SFN处理还显著抑制肺活性氧的产生,降低8-OH-dG和丙二醛水平,并逆转I/R处理大鼠肺中过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶抗氧化活性的降低。此外,SFN通过抑制Bax和裂解的caspase-3水平并增加Bcl-2表达,改善I/R诱导的大鼠肺细胞凋亡。此外,SFN处理激活了Nrf2相关的抗氧化途径,Nrf2以及下游的HO-1和NADPH醌氧化还原酶-1的核转位增加表明了这一点。总之,这些发现表明,SFN通过激活Nrf2/HO-1途径以及伴随的抗炎和抗凋亡作用,预防I/R诱导的大鼠肺部损伤。