Unraveling the protective mechanisms of Angiotensin-(1–7) in Intestinal Ischemia-Reperfusion injury: Interplay between Nrf-2/HO-1 and NF-κB/NLRP3 pathways

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-08-12 DOI:10.1016/j.lfs.2025.123898

Heba A. Abdel-Hamid , Doaa Mohamed Elroby Ali , Shimaaabdel Baset Abdel hakim , Manar Fouli Gaber Ibrahim

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引用次数: 0

Abstract

Aim

Intestinal ischemic reperfusion (I-I/R) injury is a serious clinical case with high death rate. This research assessed the influence of Angiotensin 1-7 (Ang-(1–7)) alone on the induced I-I/R injury or combined with each of nuclear factor erythroid 2 related factor 2 (Nrf-2) inhibitor (ML-385) or Mas receptor antagonist (A779). The primary objective of our study was to assess the role of Mas receptor and Nrf-2 pathway in mediating the probable protective effect of Ang-(1–7) against intestinal I/R injury.

Material and methods

Albino rats from Wistar strain were separated into; Sham group, I-I/R group, I-I/R+ Ang-(1–7), I-I/R+ Ang-(1–7)+ A779 and I-I/R+ Ang-(1–7)+ ML-385. Serum C reactive protein level (CRP) and markers of intestinal barrier malfunction were assessed. Measurements of the intestinal levels of Ang-(1–7), Angiotensin II (Ang II), angiotensin converting enzyme 2 (ACE2), in addition to the markers of oxidation, inflammation and apoptosis were taken. Also, Gene expression of heme oxygenase-1 (HO-1), Western blotting test of NOD-like receptor protein 3 (NLRP3) and immunoexpression of Nrf-2 and nuclear factor kappa B P56 (NF-κB P65) were assessed in the intestinal tissues.

Key findings

Ang-(1–7) secured against I-I/R injury through its suppressive action on oxidative stress, inflammation and apoptosis, but this protective effect was completely blocked with Mas receptor blocker and partially blocked with Nrf-2 inhibitor.

Significance

Ang-(1–7)/Mas receptors axis gave its protective influence via augmenting Nrf-2/HO-1 pathway and attenuating NF-κB/NLRP3 inflammasome pathway.

Abstract Image

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揭示血管紧张素-(1-7)在肠缺血再灌注损伤中的保护机制：Nrf-2/HO-1和NF-κ b /NLRP3通路的相互作用

目的肠缺血再灌注（I-I/R）损伤是一种严重的临床病例，死亡率高。本研究评估了血管紧张素1-7 （Ang-(1-7)）单独或联合核因子-红细胞2相关因子2 （Nrf-2）抑制剂（ML-385）或Mas受体拮抗剂（A779）对诱导的I-I/R损伤的影响。本研究的主要目的是评估Mas受体和Nrf-2通路在介导Ang-(1-7)对肠道I/R损伤的可能保护作用中的作用。材料与方法Wistar株salbino大鼠分为；虚假的集团,我/ R组,我/ R +和-(1 - 7),我/ R +和- (1 - 7)+ A779和我/ R +和- (1 - 7)+ ml - 385。评估血清C反应蛋白（CRP）水平和肠屏障功能障碍标志物。测定大鼠肠道中Ang-(1-7)、血管紧张素II （Ang II）、血管紧张素转换酶2 （ACE2）水平以及氧化、炎症和细胞凋亡标志物。检测肠组织血红素加氧酶-1 （HO-1）基因表达、nod样受体蛋白3 （NLRP3）免疫印迹检测及Nrf-2、核因子κB P56 （NF-κB P65）免疫表达。关键发现ang -(1-7)通过对氧化应激、炎症和细胞凋亡的抑制作用对I-I - i /R损伤具有保护作用，但这种保护作用被Mas受体阻滞剂完全阻断，被Nrf-2抑制剂部分阻断。意义ang -(1-7)/Mas受体轴通过增强Nrf-2/HO-1通路和减弱NF-κ b /NLRP3炎症小体通路发挥保护作用。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.