Heat stroke induces rat renal injury by endothelin receptor up-regula-tion through ERK1/2-NF-κB signaling pathway in renal arteries
10.3969/j.issn.1000-4718.2025.10.014
- VernacularTitle:热射病通过ERK1/2-NF-κB信号通路上调肾动脉内皮素受体从而引起大鼠肾损伤
- Author:
Xihan LIN
1
;
Jie LI
Author Information
1. 南方医科大学药学院,广东 广州 510515
- Publication Type:Journal Article
- Keywords:
heat stroke;
renal injury;
renal artery;
endothelin receptor;
ERK1/2-NF-κB signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(10):1993-2000
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate whether endothelin type B(ETB)and type A(ETA)receptor expression and function are up-regulated through the extracellular signal-regulated kinase 1/2(ERK1/2)-nuclear factor-κB(NF-κB)sig-naling pathway in rat renal arteries upon heat stroke(HS).METHODS:Sprague-Dawley rats were randomly divided into 4 groups:normal control group,HS group(constructed HS model),HS+U0126(ERK1/2 inhibitor,intraperitoneal injec-tion)group,and HS+DMSO(U0126 solvent,intraperitoneal injection)group.The sarafotoxin S6c and ET-1-induced dose-effect curve of renal artery constriction was generated using a microvascular tension measurement system.Moreover,the ETB and ETA receptor mRNA levels in the renal artery were detected by RT-qPCR,and the protein levels of ETB recep-tor,ETA receptor,p-ERK1/2 and p-p65 in the renal artery were assessed by Western blot.RESULTS:The HS signifi-cantly enhanced ETB and ETA receptor-mediated vasoconstriction in the renal artery(P<0.01),and increased the ETB and ETA receptor mRNA and protein levels(P<0.05)as well as the p-ERK1/2 and p-p65 protein levels(P<0.05).Intraperi-toneal U0126 injection significantly inhibited the HS effect on both ETB and ETA receptor function and expression in rat re-nal arteries.CONCLUSION:The HS up-regulates ET receptor expression and function in renal arteries through the ERK1/2-NF-κB signaling pathway,thus inducing renal injury in rats.
