Protective effects and mechanisms of dexmedetomidine on kidney donors after warm/cold ischemia in rats

ZOU Ji-feng; SHENG Hao; XIAO Ya; SONG Ya-jun

doi:10.11659/jjssx.02E024074

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Protective effects and mechanisms of dexmedetomidine on kidney donors after warm/cold ischemia in rats

Basic Research | 更新时间：2024-09-29

- Protective effects and mechanisms of dexmedetomidine on kidney donors after warm/cold ischemia in rats
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 33, Issue 9, Pages: 778-782(2024)
- 作者机构：
  
  陆军军医大学附属新桥医院泌尿外科，重庆 400037
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.02E024074
  CLC： R322.61;R617;R971.3
- Published：25 September 2024，
  
  Received：29 February 2024，
- 稿件说明：
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邹基凤,盛浩,肖亚等.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[J].局解手术学杂志,2024,33(09):778-782.

ZOU Ji-feng,SHENG Hao,XIAO Ya,et al.Protective effects and mechanisms of dexmedetomidine on kidney donors after warm/cold ischemia in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(09):778-782.
邹基凤,盛浩,肖亚等.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[J].局解手术学杂志,2024,33(09):778-782. DOI： 10.11659/jjssx.02E024074.

ZOU Ji-feng,SHENG Hao,XIAO Ya,et al.Protective effects and mechanisms of dexmedetomidine on kidney donors after warm/cold ischemia in rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(09):778-782. DOI： 10.11659/jjssx.02E024074.

摘要

目的

探索右美托咪定（Dex）对大鼠热缺血、冷缺血后供肾的保护作用及其潜在机制。

方法

将21只雄性SD大鼠随机分为对照组、模型组（0 μmol/L Dex组）和Dex组（1 μmol/L Dex组），每组7只。采用放血法处死大鼠，热缺血30 min后摘取肾，对照组供肾直接固定或-80 ℃保存，模型组和Dex组供肾分别置于含0 μmol/L Dex和1 μmol/L Dex的威斯康星大学器官保存液中4 ℃冷藏24 h，模拟供肾冷缺血状态。肾组织行HE染色后观察形态学变化并进行组织损伤评分，比色法测定N-乙酰-β-D-氨基葡萄糖苷酶（NAG）活力，TUNEL法检测细胞凋亡情况，Western blot检测受体相互作用蛋白激酶3（RIPK3）蛋白表达水平，免疫荧光法测定磷酸化混合谱系激酶结构域样假激酶（pMLKL）表达水平。

结果

对照组肾小球、肾小管无明显异常，模型组部分肾小管扩张，肾小管上皮细胞扁平，Dex组肾小管损伤较模型组缓解。与对照组比较，模型组和Dex组肾损伤评分、NAG活性升高，TUNEL阳性凋亡细胞数增多，pMLKL和RIPK3表达水平增加（

0.05）。与模型组比较，Dex组肾损伤评分、NAG活性降低，TUNEL阳性凋亡细胞数减少，pMLKL表达水平下降（

0.05）。

结论

Dex对大鼠热缺血、冷缺血后供肾具有保护作用，其机制与减少细胞凋亡、抑制坏死性凋亡有关。

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 preservation 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 （

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 （

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.

关键词

热缺血冷缺血右美托咪定肾移植器官保护

Keywords

warm ischemiacold ischemiadexmedetomidinekidney transplantationorgan protection

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