Protective Effect and Mechanism of Creatine Against Renal Ischemia-Reperfusion Injury in Mice
LU Peng
CHI Kaikai
JING Zhaopeng
JING Gaopeng
WANG Suogang
XIE Shiyang
CHEN Zhu
Abstract：Objective To investigate the expression and protective effect of creatine in warm ischemia-reperfusion injury in mice.Methods The warm ischemia-reperfusion injury model was established in twenty four C57BL/6 mice,and were randomly divided into sham-operated group(sham,6 mice),ischemia-reperfusion group(I/R,12 mice)and creatine pretreatment group(Cre,6 mice).Transcriptomics and metabolomics detections were employed in the sham and I/R(6 mice)groups.The evaluation parameters in the sham,I/R(6 mice)and Cre groups included serum urea nitrogen(BUN)and cystatin C(Cys-C)levels by the automated biochemical analyzer,the pathological changes by hematoxylin-eosin staining(HE),expression of guanidinoacetate methyltransferase(GAMT)by immunohistochemistry(IHC)and western blot(WB),and levels of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)in the kidney tissues.T-test was used for comparison between two groups.Results In the I/R group at 24 hours and the sham group,the serum BUN and Cys-C levels in the I/R group were increased(P＜0.05).HE staining showed that the renal injury score in the I/R group was increased(P＜0.05).The MDA level in the renal tissues of the I/R group increased,while the SOD activity decreased(P＜0.05).In the I/R group at 6 hours and the sham group,metabolomics mass spectrometry analysis showed that the creatine level in the I/R group decreased(P＜0.05),and transcriptome sequencing revealed that the expression of GAMT in the I/R group was downregulated(P＜0.05).In the I/R group at 6,24 hours and the sham group,the quantitative scores using WB and IHC showed that the expression of GAMT in the I/R group was decreased(P＜0.05).Twenty-four hours after intramuscular injection of creatine in the I/R group and the Cre group,the levels of BUN and Cys-C in the Cre group were lower(P＜0.05).HE staining showed that the renal injury score in the Cre group was lower than that in the IR group(P＜0.05).The MDA level in the renal tissues of the Cre group was decreased,while the SOD activity was increased(P＜0.05).Conclusion The expressions of creatine and GAMT decrease in warm ischemia-reperfusion injury,and supplement of creatine could alleviate warm ischemia-reperfusion injury in mice.
Keywords：ischemia-reperfusion injuryguanidinoacetate methyltransferasecreatine
Publication Date：2026-05-13
Online Publishing Date：2026-09-12(First online date of this platform, not the publication date of the document)
Pages：5( 1563-1567 )