The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat

Background: Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury rem...

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Main Authors: Chen Jin, Wen-Liang Fu, Dong-Dong Zhang, Wei-Wei Xing, Wen-Rong Xia, Zhao Wei, Min-Ji Zou, Xiao-Ming Zhu, Dong-Gang Xu
Format: Article
Language:English
Published: Elsevier 2019-02-01
Series:Biomedical Journal
Online Access:http://www.sciencedirect.com/science/article/pii/S2319417018302932
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author Chen Jin
Wen-Liang Fu
Dong-Dong Zhang
Wei-Wei Xing
Wen-Rong Xia
Zhao Wei
Min-Ji Zou
Xiao-Ming Zhu
Dong-Gang Xu
author_facet Chen Jin
Wen-Liang Fu
Dong-Dong Zhang
Wei-Wei Xing
Wen-Rong Xia
Zhao Wei
Min-Ji Zou
Xiao-Ming Zhu
Dong-Gang Xu
author_sort Chen Jin
collection DOAJ
description Background: Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. Methods: The rat model of intestinal I/R was induced by occlusion (for 60 min) and reopening (for 60 min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10 mg/kgIL-1Ra + I/R (C1),20 mg/kgIL-1Ra + I/R (C2), and30 mg/kgIL-1Ra + I/R (C3). Results: In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1β, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. Conclusion: IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury. Keywords: Interleukin 1 receptor antagonist (IL-1Ra), Intestinal ischemia reperfusion injury, Protective effect, Nrf2/HO-1, Clinical application
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spelling doaj.art-c1f64d9e12264057bb6935542d3175f82022-12-22T02:19:45ZengElsevierBiomedical Journal2319-41702019-02-014213645The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in ratChen Jin0Wen-Liang Fu1Dong-Dong Zhang2Wei-Wei Xing3Wen-Rong Xia4Zhao Wei5Min-Ji Zou6Xiao-Ming Zhu7Dong-Gang Xu8Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR China; Anhui Medical University, Hefei, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR ChinaInstitute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing, PR China; Anhui Medical University, Hefei, PR China; Corresponding author. Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, PR China.Background: Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. Methods: The rat model of intestinal I/R was induced by occlusion (for 60 min) and reopening (for 60 min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10 mg/kgIL-1Ra + I/R (C1),20 mg/kgIL-1Ra + I/R (C2), and30 mg/kgIL-1Ra + I/R (C3). Results: In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1β, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. Conclusion: IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury. Keywords: Interleukin 1 receptor antagonist (IL-1Ra), Intestinal ischemia reperfusion injury, Protective effect, Nrf2/HO-1, Clinical applicationhttp://www.sciencedirect.com/science/article/pii/S2319417018302932
spellingShingle Chen Jin
Wen-Liang Fu
Dong-Dong Zhang
Wei-Wei Xing
Wen-Rong Xia
Zhao Wei
Min-Ji Zou
Xiao-Ming Zhu
Dong-Gang Xu
The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
Biomedical Journal
title The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
title_full The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
title_fullStr The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
title_full_unstemmed The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
title_short The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
title_sort protective role of il 1ra on intestinal ischemia reperfusion injury by anti oxidative stress via nrf2 ho 1 pathway in rat
url http://www.sciencedirect.com/science/article/pii/S2319417018302932
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