MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

Download Full-text

CEBPA-AS1 knockdown alleviates OGD/R-induced neuron cell damage by the miR-24-3p/BOK axis

Molecular and Cellular Biology ◽

10.1128/mcb.00065-21 ◽

2021 ◽

Author(s):

Guangfu Di ◽

Xinjie Yang ◽

Feng Cheng ◽

Hua Liu ◽

Min Xu

Keyword(s):

Oxidative Stress ◽

Noncoding Rna ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Protective Role ◽

Luciferase Reporter ◽

Induced Neuron ◽

Induced Apoptosis

Cerebral ischemia/reperfusion (I/R) can lead to serious brain function impairments. Long noncoding RNA (lncRNA) CCAAT enhancer binding protein α antisense RNA 1 (CEBPA-AS1) was shown to be upregulated in human ischemic stroke. This work investigated the function and mechanism of CEBPA-AS1 in I/R. An oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce I/R injury in SH-SY5Y cells in vitro. RT-qPCR examined the expression of CEBPA-AS1, microRNA-24-3p (miR-24-3p), and Bcl-2-related ovarian killer (Bok). The cell viability, apoptosis, oxidative stress in OGD/R-treated cells were detected using CCK-8, flow cytometry, western blot, ELISA assays. The relationship among genes was tested by RNA pulldown and luciferase reporter assays. We found that OGD/R upregulated CEBPA-AS1 expression in SH-SY5Y cells. Functionally, CEBPA-AS1 depletion ameliorated OGD/R-induced apoptosis and oxidative stress in SH-SY5Y cells by reducing ROS production and superoxide dismutase (SOD) and glutathione (GSH). Mechanistic investigations indicated that CEBPA-AS1 acts as a sponge for miR-24-3p, and miR-24-3p binds to the BOK. Moreover, miR-24-3p upregulation or BOK downregulation antagonized the protective role of CEBPA-AS1 depletion in SH-SY5Y cells exposed to OGD/R. Overall, downregulation of CEBPA-AS1 exerts protective functions against OGD/R-induced injury by targeting the miR-24-3p/BOK axis.

Download Full-text

Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

Neural Plasticity ◽

10.1155/2019/8798069 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Xiangli Yan ◽

Aiming Yu ◽

Haozhen Zheng ◽

Shengxin Wang ◽

Yingying He ◽

...

Keyword(s):

Oxidative Stress ◽

Neuronal Apoptosis ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Pathological Process ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

Positive Effects ◽

Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

Download Full-text

miR-182-5p and miR-378a-3p regulate ferroptosis in I/R-induced renal injury

Cell Death and Disease ◽

10.1038/s41419-020-03135-z ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Chenguang Ding ◽

Xiaoming Ding ◽

Jin Zheng ◽

Bo Wang ◽

Yang Li ◽

...

Keyword(s):

Cell Death ◽

Renal Injury ◽

Molecular Mechanisms ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Luciferase Reporter ◽

Renal Tubular Cell ◽

In Cells

Abstract Renal tubular cell death is the key factor of the pathogenesis of ischemia/reperfusion (I/R) kidney injury. Ferroptosis is a type of regulated cell death (RCD) found in various diseases. However, the underlying molecular mechanisms related to ferroptosis in renal I/R injury remain unclear. In the present study, we investigated the regulatory role of microRNAs on ferroptosis in I/R-induced renal injury. We established the I/R-induced renal injury model in rats, and H/R induced HK-2 cells injury in vitro. CCK-8 was used to measure cell viability. Fe2+ and ROS levels were assayed to evaluate the activation of ferroptosis. We performed RNA sequencing to profile the miRNAs expression in H/R-induced injury and ferroptosis. Western blot analysis was used to detect the protein expression. qRT-PCR was used to detect the mRNA and miRNA levels in cells and tissues. We further used luciferase reporter assay to verify the direct targeting effect of miRNA. We found that ischemia/reperfusion-induced ferroptosis in rat’s kidney. We identified that miR-182-5p and miR-378a-3p were upregulated in the ferroptosis and H/R-induced injury, and correlates reversely with glutathione peroxidases 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression in renal I/R injury tissues, respectively. In vitro studies showed that miR-182-5p and miR-378a-3p induced ferroptosis in cells. We further found that miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3′UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced renal injury in rats. In conclusion, we demonstrated that I/R induced upregulation of miR-182-5p and miR-378a-3p, leading to activation of ferroptosis in renal injury through downregulation of GPX4 and SLC7A11.

Download Full-text

MicroRNA-429/Cxcl1 Axis Protective Against Oxygen Glucose Deprivation/Reoxygenation-Induced Injury in Brain Microvascular Endothelial Cells

Dose-Response ◽

10.1177/1559325820913785 ◽

2020 ◽

Vol 18 (2) ◽

pp. 155932582091378

Author(s):

Jun Leng ◽

Wei Liu ◽

Li Li ◽

Fang Yue Wei ◽

Meng Tian ◽

...

Keyword(s):

Endothelial Cells ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Luciferase Reporter ◽

Microvascular Endothelial Cells ◽

Oxygen Glucose Deprivation ◽

Brain Microvascular Endothelial Cells ◽

Public Data ◽

Microvascular Endothelial

Objective: The objective of the present work was to study the role of Cxcl1 in cerebral ischemia–reperfusion (I/R) injury and to in-depth explore its pathogenesis. Methods: The expression of Cxcl1 based on the public data was analyzed. Then, we constructed an oxygen glucose deprivation/reoxygenation (OGD/R) model in vitro using mice brain microvascular endothelial cells (BMECs) to simulate cerebral I/R in vivo. Results: The results of quantitative real-time polymerase chain reaction assay uncovered that Cxcl1 showed higher expression while miR-429 showed lower expression in BMECs damaged by OGD/R, whereas overexpression of Cxcl1 or inhibition of miR-429 expression can strengthen this effect. Hereafter, through dual luciferase reporter assay, we verified that miR-429 directly targets Cxcl1 and negatively regulates Cxcl1 expression. Furthermore, the results also revealed that overexpression of Cxcl1 can reverse the miR-429-mediated effects. Conclusion: We concluded that miR-429 exerts protective effects against OGD/R-induce injury in vitro through modulation of Cxcl1 and nuclear factor kinase B pathway, hoping provide a new view on the pathogenesis of cerebral I/R injury and a feasible potential therapeutic target.

Download Full-text

Targeted Delivery of Intranasally Administered Cyclovirobuxine D Liposomes to Brain for Treatment Cerebral Ischemia-Reperfusion Injury via Anti-oxidative Stress and Activating Autophagy

10.21203/rs.3.rs-966870/v2 ◽

2022 ◽

Author(s):

Tuo Liu ◽

Fang Yang ◽

Xiangyi Lu ◽

Chang Liu ◽

Yang Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion ◽

Protein Expressions ◽

Cerebral Ischemia Reperfusion Injury ◽

Ht22 Cell

Abstract The lack of effective therapy mandates development of treatment for cerebral ischemia-reperfusion injury (CIRI. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study focused on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. In order to evaluate these, the CIRI rat model was induced by middle cerebral artery occlusion (MCAO)-reperfusion. Pharmacological evaluation was assessed in vivo by general indexs, neurobehavioral scores, triphenyl tetrazolium chloride (TTC) staining, histopathological staining (HE staining and Nissl staining), small animal magnetic resonance imaging, biochemical assay and Western blot. The results show that CVBD liposomes alleviated pathological damage of brain. Futhermore, the protective effect of CVBD liposomes on OGD/R-injured HT22 cell was investigated by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions (LC3, p62 and Beclin 1) were analyzed by Western blot. Meanwhile, the classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulated mechanism of CVBD brain-targeted liposomes in treating CIRI. In cell model of oxygen and glucose deprivation/re-oxygenation, CVBD liposomes increased cell viability and decreased ROS level. CVBD liposomes improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated to anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro, showing a great potential in treating CIRI in clinic.

Download Full-text

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8768327 ◽

2019 ◽

Vol 2019 ◽

pp. 1-18 ◽

Cited By ~ 5

Author(s):

Jing Zeng ◽

Long Zhu ◽

Jing Liu ◽

Tao Zhu ◽

Zhaohui Xie ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Luciferase Reporter ◽

Neuroprotective Effects ◽

Stress Injury ◽

Oxidative Stress Injury

Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects. However, the mechanism of action of metformin in ischemic stroke is unclear. Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury. It has been reported that metformin is associated with stroke risk in the clinical population. This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro. Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia. The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx). First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress. It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R. Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2). The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay. lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression. The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro. In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis. These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.

Download Full-text

miR-325-3p Protects Neurons from Oxygen-Glucose Deprivation and Reoxygenation Injury via Inhibition of RIP3

Developmental Neuroscience ◽

10.1159/000509108 ◽

2020 ◽

pp. 1-11

Author(s):

Song Yi ◽

Chuqin Zhang ◽

Na Li ◽

Yajing Fu ◽

Hongkun Li ◽

...

Keyword(s):

Western Blot ◽

Mapk Pathway ◽

Ischemia Reperfusion ◽

Neuronal Injury ◽

Glucose Deprivation ◽

Mitogen Activated Protein Kinase ◽

Luciferase Reporter ◽

Oxygen Glucose Deprivation ◽

Loss Of Function

Objective: Recent reports have corroborated that microRNAs (miRs) are related to the pathological changes of cerebral ischemia-reperfusion (CIR) induced injury. This work aimed to unearth the role and potential mechanism of miR-325-3p in regulating neuronal survival in CIR injury. Methods: To conduct this investigation, we established an in vitro model of CIR injury by subjecting neurons to oxygen-glucose deprivation and reoxygenation (OGD/R). Gain and loss of function of miR-325-3p and receptor-interacting serine-threonine kinase 3 (RIP3) in neurons were performed to observe its effect on cell apoptosis and the release of lactate dehydrogenase. The levels of miR-325-3p and RIP3 in neurons were detected by qRT-PCR. Western blot was employed to inspect the levels of caspase3, Bax, and Bcl-2, as well as p38 and JNK phosphorylation. The relationship between miR-325-3p and RIP3 was detected by TargetScan and validated by dual-luciferase reporter assay. Results: Firstly, miR-325-3p expression was obviously downregulated while RIP3 expression was upregulated in neurons following OGD/R treatment. Overexpressed miR-325-3p or downexpressed RIP3 ameliorated OGD/R-induced neuronal injury. Besides, RIP3 was a direct target mRNA of miR-325-3p. Additionally, Western blot revealed the mitogen-activated protein kinase (MAPK) pathway was involved in the regulation of miR-325-3p on OGD/R-induced neuronal injury. Furthermore, miR-325-3p was verified to hinder OGD/R-induced neuronal injury through downregulating RIP3. Conclusion: This study demonstrated that miR-325-3p targets RIP3 to inactivate the MAPK pathway, thereby protecting neurons against OGD/R-induced injury.

Download Full-text

The Protective Effect of Cyanidin-3-Glucoside on Myocardial Ischemia-Reperfusion Injury through Ferroptosis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/8880141 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Xin Shan ◽

Zhi-Yang Lv ◽

Meng-Jiao Yin ◽

Jing Chen ◽

Jie Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Protective Effect ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

H9c2 Cells ◽

St Segment Elevation ◽

Myocardial Ischemia Reperfusion

This study was conducted to estimate the protective effect of Cyanidin-3-glucoside (C3G) on myocardial ischemia-reperfusion (IR) injury and to explore its mechanism. The rats were subjected to left anterior descending ligation and perfusion surgery. In vitro experiments were performed on H9c2 cells using the oxygen-glucose deprivation/reoxygenation (OGD/R) model. The results showed the administration of C3G reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. C3G could inhibit the protein levels of USP19 and LC3II. C3G promoted K11-linked ubiquitination of Beclin1. Further evidence that C3G reduced ferroptosis and ameliorated myocardial I/R injury was demonstrated with the ferroptosis promoter RSL3. Taken together, C3G could be a potential agent to protect myocardium from myocardial I/R injury.

Download Full-text

The Effects of Hypoxia-Reoxygenation in Mouse Digital Flexor Tendon-Derived Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7305392 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Chen Chen ◽

Wei Feng Mao ◽

Ya Fang Wu

Keyword(s):

Oxidative Stress ◽

Cell Growth ◽

Cell Viability ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mitochondrial Activity ◽

Cellular Apoptosis ◽

High Concentrations ◽

Related Proteins ◽

In Cells

Objective. Ischemia-reperfusion injury refers to the exacerbated and irreversible tissue damage caused by blood flow restoration after a period of ischemia. The hypoxia-reoxygenation (H/R) model in vitro is ideal for studying ischemia-reperfusion injury at the cellular level. We employed this model and investigated the effects of cobalt chloride- (CoCl2-) induced H/R in cells derived from mouse digital flexor tendons. Materials and Methods. Various H/R conditions were simulated via treatment of tendon-derived cells with different concentrations of CoCl2 for 24 h, followed by removal of CoCl2 to restore a normal oxygen state for up to 96 h. Cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay. Cell growth was determined via observation of cell morphology and proliferation. Oxidative stress markers and mitochondrial activity were detected. The expression levels of hypoxia-inducible factor- (HIF-) 1α, vascular endothelial growth factor-A (VEGF-A), collagen I, and collagen III were determined using Western blot (WB), real-time PCR, and immunofluorescence staining. Cellular apoptosis was analyzed via flow cytometry, and the expression of apoptosis-related proteins Bax and bcl-2 was examined using WB. Results. The cells treated with low concentrations of CoCl2 showed significantly increased cell viability after reoxygenation. The increase in cell viability was even more pronounced in cells that had been treated with high concentrations of CoCl2. Under H/R conditions, cell morphology and growth were unchanged, while oxidative stress reaction was induced and mitochondrial activity was increased. H/R exerted opposite effects on the expression of HIF-1α mRNA and protein. Meanwhile, the expression of VEGF-A was upregulated, whereas collagen type I and type III were significantly downregulated. The level of cellular apoptosis did not show significant changes during H/R, despite the significantly increased Bax protein and reduced bcl-2 protein levels that led to an increase in the Bax/bcl-2 ratio during reoxygenation. Conclusions. Tendon-derived cells were highly tolerant to the hypoxic environments induced by CoCl2. Reoxygenation after hypoxia preconditioning promoted cell viability, especially in cells treated with high concentrations of CoCl2. H/R conditions caused oxidative stress responses but did not affect cell growth. The H/R process had a notable impact on collagen production and expression of apoptosis-related proteins by tendon-derived cells, while the level of cellular apoptosis remained unchanged.

Download Full-text

Resveratrol Alleviates Vascular Endothelial Damage Caused by Lower-Extremity Ischemia Reperfusion (I/R) through Regulating Keap1/Nrf2 Signaling-Mediated Oxidative Stress

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5556603 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xiaojun Song ◽

Zhili Liu ◽

Rong Zeng ◽

Jiang Shao ◽

Yuehong Zheng ◽

...

Keyword(s):

Oxidative Stress ◽

Lower Extremity ◽

Cell Viability ◽

Ischemia Reperfusion ◽

Endothelial Damage ◽

Pathological State ◽

Vascular Endothelial ◽

Protective Effects ◽

Commercial Kits

The present study aims to investigate the protective effects of Resveratrol (RSV) against vascular endothelial damage caused by lower-extremity I/R and the underlying preliminary mechanism. The in vitro hypoxia reoxygenation (HR) model was established on HUVECs. Lower-extremity I/R model was established on rats followed by being treated with RSV and the pathological state of artery was evaluated by HE and EVG staining, while the apoptotic state of artery was detected by TUNEL assay. The cell viability was detected by MTT assay and the apoptotic state of cells was determined by Hoechst test and flow cytometry assay. DCFH-DA staining was used to measure the level of ROS and the production of MDA and SOD was measured by commercial kits. The expression level of Nrf2, Keap1, HO-1, Bcl-2, Bax, and Caspase-3 in cells was determined by Western blot. Nrf2 was knocked down by siRNA technology. Overall, our data indicated that increased cell viability, declined apoptotic rate, and alleviated oxidative stress were observed in RSV treated HR HUVECs, which were significantly reversed by knocking down Nrf2. Animal experiment revealed that the pathological and apoptotic state of femoral artery were dramatically ameliorated by the treatment of RSV, accompanied by the alleviated oxidative stress, which were abolished by the co-administration of ML385, an inhibitor of Nrf2. Taken together, our data revealed that RSV might alleviate vascular endothelial injury induced by lower-extremity I/R injury through regulating Keap1/Nrf2 signaling-mediated oxidative stress.

Download Full-text