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Updated: May 9, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat
Hua Yang1, Heng Li, Zhendi Wang
1Department of Urologic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background:
Glucagon-like peptide-1 receptor (GLP-1R) activation exerts protective effects against reactive oxygen species by inducing the oxidative defense gene heme oxygenase-1 (HO-1), and provides protection in mice against transient focal cerebral ischemia and ischemia-reperfusion injury in the rat heart. GLP-1R is also expressed in the kidney, but it is unknown whether GLP-1R activation is able to protect against ischemia-reperfusion injury in the rat kidney.
Materials And Methods:
We used a rat model of renal ischemia-reperfusion injury. The rats were pretreated with the GLP-1R agonist, exendin-4 before reperfusion. We used real-time polymerase chain reaction to evaluate expression of the oxidative defense gene HO-1 and Western blot analysis for HO-1 and GLP-1R. Renal function was assessed at baseline and 24 and 72 h after reperfusion. The kidneys were processed for histologic and morphometric analysis, caspase-3, and ED1 immunohistochemistry at 72 h. The degree of apoptosis of the renal tubular cells was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end labeling assays.
Results:
Exendin-4 pretreatment resulted in GLP-1R activation and upregulation of HO-1. Preconditional activation of GLP-1R significantly improved the serum creatinine levels compared with vehicle (P < 0.05). Furthermore, tissue injury, caspase-3 and ED1 expression, and apoptosis were less severe, as quantified by application of a standardized histologic scoring system in a blinded manner.
Conclusions:
These results have demonstrated that preconditional activation of the GLP-1R with exendin-4 in the kidney significantly protected against ischemia-reperfusion injury in rats by increasing HO-1 expression.
Insights
Glucagon-like peptide-1 receptor (GLP-1R) activation protects the kidney from injury. Pretreatment with exendin-4 increased heme oxygenase-1 (HO-1) expression, reducing damage and improving function after ischemia-reperfusion.
Area of Science:
- Nephrology
- Molecular Biology
- Cardiovascular Research
Background:
- Glucagon-like peptide-1 receptor (GLP-1R) activation protects against oxidative stress and injury in various organs.
- GLP-1R is present in the kidney, but its role in renal ischemia-reperfusion injury is not well understood.
Purpose of the Study:
- To investigate the protective effects of GLP-1R activation against renal ischemia-reperfusion injury in a rat model.
- To determine if GLP-1R activation upregulates the oxidative defense gene heme oxygenase-1 (HO-1) in the kidney.
Main Methods:
- Rats underwent renal ischemia-reperfusion injury and were pretreated with the GLP-1R agonist exendin-4.
- Real-time PCR and Western blot were used to assess HO-1 and GLP-1R expression.
- Renal function, histology, apoptosis, and inflammatory markers were evaluated post-reperfusion.
Main Results:
- Exendin-4 pretreatment activated GLP-1R and upregulated HO-1 expression.
- Significant improvement in serum creatinine levels was observed in exendin-4 treated rats.
- Reduced tissue injury, caspase-3 and ED1 expression, and apoptosis were noted.
Conclusions:
- Preconditional activation of GLP-1R with exendin-4 confers significant protection against renal ischemia-reperfusion injury in rats.
- The protective mechanism involves the upregulation of heme oxygenase-1 (HO-1) expression.
