中华灾害救援医学2025，Vol.12Issue(10)：1140-1145,6.DOI:10.13919/j.issn.2095-6274.ZHJY202506045
Nrf2-Keap1-ARE信号通路在大鼠创伤性肺损伤中的抗氧化应激作用及其调控机制的研究
Antioxidant Stress Role and Regulatory Mechanism of the Nrf2-Keap1-ARE Signaling Pathway in Traumatic Lung Injury in Rats
摘要
Abstract
Objective To investigate the antioxidant stress role and regulatory mechanism of the Nrf2-Keap1-ARE signaling pathway in traumatic lung injury(TLI)in rats.Methods Healthy male Wistar rats were randomly divided into a control group,a TLI model group,and an Nrf2 agonist pretreatment group.The TLI model was established by impacting the right chest using a biological impact machine.Rats in the Nrf2 agonist pretreatment group received an intraperitoneal injection of the specific Nrf2 agonist sulforaphane(5 mg/kg)30 minutes before modeling.At 24 hours post-modeling,arterial blood gas parameters were measured,the lung wet/dry(W/D)weight ratio was calculated,and the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)were determined.The mRNA expression levels of Keap1,heme oxygenase-1(HO-1),and NAD(P)H quinone oxidoreductase 1(NQO1)in lung tissue were detected by real-time quantita-tive PCR,and the expression of Nrf2 nuclear protein was detected by Western blot.Results Compared with the control group,the TLI group showed significantly decreased arterial blood pH and PaO2,and significantly increased PaCO2,lung W/D ratio,and MPO activity,while SOD activity was significantly decreased(P<0.05).Concurrently,the mRNA expres-sion of Keap1 in lung tissue was up-regulated,while the nuclear protein expression of Nrf2 and the mRNA expression of its downstream target genes HO-1 and NQO1 were down-regulated in the TLI group(P<0.05).Compared with the TLI group,Nrf2 agonist pretreatment effectively reversed the aforementioned indicators:arte-rial blood oxygenation improved,pulmonary edema alleviated,MPO activity decreased,and SOD activity increased.At the molecular level,Keap1 mRNA expression was inhibited,Nrf2 nuclear protein accumulated,and the mRNA expression of HO-1 and NQO1 was up-regulated(P<0.05).Conclusions Oxidative stress is an important pathogenesis of TLI.Activation of the Nrf2-Keap1-ARE signaling pathway can inhibit Keap1 expression,promote Nrf2 nuclear translocation,thereby up-regulating the expression of downstream antioxidant genes such as HO-1 and NQO1,ultimately alleviating ox-idative stress injury and improving lung function after TLI.关键词
动物实验/创伤性肺损伤/氧化应激Key words
animals,laboratory/traumatic lung injury/oxidative stress引用本文复制引用
崔建斌,刘晓辉,朱宇婷,郑珊珊,刘丰瑜,焦海涛..Nrf2-Keap1-ARE信号通路在大鼠创伤性肺损伤中的抗氧化应激作用及其调控机制的研究[J].中华灾害救援医学,2025,12(10):1140-1145,6.基金项目
山东省潍坊市2024年科技发展医学类计划项目(2024YX095) （2024YX095）
