Antioxidant Stress Role and Regulatory Mechanism of the Nrf2-Keap1-ARE Signaling Pathway in Traumatic Lung Injury in Rats

CUI Jianbin; LIU Xiaohui; ZHU Yuting; ZHENG Shanshan; LIU Fengyu; JIAO Haitao

doi:10.13919/j.issn.2095-6274.ZHJY202506045

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.