Protective effects and mechanisms of dexmedetomidine on kidney donors after warm/cold ischemia in rats
- VernacularTitle:右美托咪定对大鼠热/冷缺血后供肾的保护作用及机制研究
- Author:
Ji-Feng ZOU
1
;
Hao SHENG
;
Ya XIAO
;
Ya-Jun SONG
Author Information
- Keywords: warm ischemia; cold ischemia; dexmedetomidine; kidney transplantation; organ protection
- From: Journal of Regional Anatomy and Operative Surgery 2024;33(9):778-783
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the protective effects and mechanisms of dexmedetomidine(Dex)on kidney donors after warm ischemia and cold ischemia in rats.Methods A total of twenty-one male SD rats were randomly allocated into the control group,the model group(0 μmol/L Dex group)and the Dex group(1 μmol/L Dex group),with 7 rats in each group.All the rats were killed by bloodletting,the kidneys were extracted after 30 minutes of warm ischemia,and the kidneys of the control group were directly fixed or preserved at-80 ℃.The kidney donors of the model group and the Dex group were respectively refrigerated in the university of Wisconsin organ preserva-tion solution containing 0 μmol/L Dex and 1 μmol/L Dex at 4 ℃ for 24 hours,to simulate the cold ischemia state of the kidney donors.HE staining was performed to observe the morphological changes and the tissue injury score was conducted.The activity of N-acetyl-β-D-glucosaminase(NAG)was determined by colorimetry,the apoptosis level was detected by TUNEL,the expression level of receptor-interacting protein kinase 3(RIPK3)was detected by Western blot,and the expression level of phosphorylation mixed lineage kinase domain like protein(pMLKL)was determined by immunofluorescence method.Results In the control group,there were no obvious abnormalities in glomerular or renal tubules.In the model group,some renal tubules were dilated and tubular epithelial cells were flattened.Compared with the model group,the damage of renal tubules in the Dex group was alleviated.Compared with the control group,kidney injury score,NAG activity,TUNEL positive cell number,pMLKL and RIPK3 expression levels were increased in the model group and the Dex group(P<0.05).Compared with the model group,kidney injury score,NAG activity,TUNEL positive cell number,and pMLKL expression level were decreased in the Dex group(P<0.05).Conclusion Dex has protective effects on kidney donors after warm ischemia and cold ischemia,and its mechanism is related to reducing apoptosis and inhibiting necroptosis.