Effects of dexmedetomidine at different concentrations on donor kidneys after cardiac death in rats

Xiangfeng LIU; Zhengwei XUE; Zhigang QIN; Jieyu LI; Yirong LI; Lin CHEN; Peng LI; Jianteng GU

doi:10.16016/j.2097-0927.202307096

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Effects of dexmedetomidine at different concentrations on donor kidneys after cardiac death in rats

Basic Medicine | 更新时间：2026-01-09

- Effects of dexmedetomidine at different concentrations on donor kidneys after cardiac death in rats
- Journal of Army Medical University Vol. 45, Issue 20, Pages: 2179-2188(2023)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院麻醉科
  2.400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系生药学与中药学教研室
- 作者简介：
- 基金信息：
  
  the Chongqing Talent Program(CQYC20220303588);the Talent Foundation of Army Medical University(XZ-2019-505-028)
- DOI：10.16016/j.2097-0927.202307096
  CLC： R322.61;R617;R971.2
- Received：18 July 2023，
  
  Revised：2023-09-16，
  
  Published：30 October 2023
- 稿件说明：
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Xiangfeng LIU, Zhengwei XUE, Zhigang QIN, et al. Effects of dexmedetomidine at different concentrations on donor kidneys after cardiac death in rats[J]. Journal of Army Medical University, 2023, 45(20): 2179-2188.
DOI：

Xiangfeng LIU, Zhengwei XUE, Zhigang QIN, et al. Effects of dexmedetomidine at different concentrations on donor kidneys after cardiac death in rats[J]. Journal of Army Medical University, 2023, 45(20): 2179-2188. DOI： 10.16016/j.2097-0927.202307096.

摘要

目的

实验比较不同浓度右美托咪定(Dexmedetomidine，Dex)对大鼠心脏死亡后供体(donation after circulatory death，DCD)静态冷藏期肾脏的保护作用，从而探讨Dex适宜剂量。

方法

将40只雄性SD大鼠随机分为(

=5)：对照组(NC组)、模型组(0 nmol/L Dex组)和6个不同浓度Dex组(0.1、1、10、100、1 000、10 000 nmol/L Dex组)。大鼠麻醉和肝素化后放血法处死。热缺血30 min时：NC组灌注等体积的生理盐水，摘取肾脏、固定、-80 ℃保存；其余按分组浓度灌注含Dex的威斯康星大学器官保存液(University of Wisconsin solution，UW液)，摘取肾脏、并置于相应保存液4 ℃保存24 h模拟供肾静态冷藏。光镜观察肾组织形态学变化，免疫组化法测定Caspase-3和肾组织损伤因子1(kidney injury molecule-1，KIM-1)的表达水平，比色法测定NAG活力，羟胺法测定T-SOD活力、TBA法测定MDA含量，RT-qPCR检测炎症相关因子IL-6、TNF-α的mRNA扩增水平。

结果

① 与NC组比较：0 nmol/L Dex组肾损伤评分、Caspase-3和KIM-1水平、NAG活力、MDA含量和IL-6 mRNA扩增水平增加，T-SOD活力降低(

0.05)。②与0 nmol/L Dex组比较：100、1000 nmol/L Dex组肾损伤评分显著降低[(1.33±0.26)分、(1.30±0.16)分

(2.14±0.34)分，

0.05)

]

；1、10、100、1 000 nmol/L Dex组KIM-1的表达水平降低(

0.05)；100、1 000 nmol/L Dex组NAG活力下降(

0.05)，Caspase-3表达水平降低(

0.05)；1、10、100、1 000、10 000 nmol/L Dex组MDA表达量降低(

0.05)；0.1、1、10、100、1 000 nmol/L Dex组IL-6的mRNA水平降低(

0.05)；0.1、1、10、100、1 000、10 000 nmol/L Dex组TNF-α的mRNA水平降低(

0.05)。③与0.1 nmol/L Dex组比较：100、1 000 nmol/L Dex组KIM-1的表达水平显著降低[(0.19±0.01)、(0.18±0.02)

(0.25±0.02)，

0.05)

]

，MDA表达量显著降低(

0.05)；10、100、1 000 nmol/L Dex组IL-6、TNF-α水平显著降低(

0.05)。④与1、10 nmol/L Dex组比较：100、1 000 nmol/L Dex组TNF-α水平降低(

0.05)。

⑤与0、0.1、10 nmol/L Dex组比较：1 000 nmol/L Dex组SOD活力增加(

0.05)。

结论

Dex对大鼠DCD供肾的保护效应随浓度增加而增强，100、1 000 nmol/L Dex剂量保护效果最佳；其机制可能涉及减少细胞凋亡、抑制炎症反应和抗氧化应激。

Abstract

Objective

To compare the protective effects of dexmedetomidine (Dex) at different concentrations on donor kidneys from donation after circulatory death (DCD) in rats during static cold storage

and to investigate the appropriate dose of Dex in protection of donor kidneys of DCD.

Methods

Forty male SD rats were randomly divided into control group (NC group)

model group (0 nmol/L Dex) and 6 dosed Dex groups (0.1

100

1 000 and 10 000 nmol/L)

with 5 animals in each group. All rats were euthanized after anesthetization and intravenous injection of heparin. In 30 min after warm ischemia

renal perfusion was given with normal saline to the rats of the NC group

and with the University of Wisconsin organ preservation solution (UW solution) containing corresponding concentrations of Dex to the rest groups. In the NC group

the kidneys were harvested

fixed directly and stored at -80 ℃. The kidneys of the other groups were harvested after infusion of UW solution containing different concentrations of Dex and then stored in the corresponding preservation solution at 4 ℃ for 24 h to simulate static cold storage of donor kidneys. The morphological changes of renal tissues were observed by light microscopy. The expression levels of Caspase-3 and kidney injury molecule-1 (KIM-1) were determined by immunohistochemical staining. The MDA content

T-SOD activity and NAG level were determined by corresponding reagent kits. The mRNA levels of inflammation-related factors IL-6 and TNF-α were detected by real-time quantitative PCR.

Results

① The 0 nmol/L Dex group had significantly increased renal injury score

Caspase-3 and KIM-1 levels

enhanced NAG activity

and elevated MDA content and IL-6 mRNA level

decreased T-SOD activity than the NC group (

0.05). ② In comparison with the 0 nmol/L Dex group

the renal injury score was reduced in the 100 and 1 000 nmol/L groups (1.33±0.26 and 1.30±0.16

2.14±0.34

0.05)

the expression level of KIM-1 was declined in the 1

100 and 1 000 nmol/L Dex groups (

0.05)

NAG activity and Caspase-3 expression were decreased in the 100 and 1 000 nmol/L groups (

0.05)

decreased MDA content was observed in all dose groups except the 0.1 nmol/L Dex group(

0.05)

decreased mRNA levels of IL-6 was in all dose groups except the 10 000 nmol/L Dex group(

0.05)

and declined mRNA levels of TNF-α was seen in all dose groups (

0.05). ③Compared with 0.1 nmol/L Dex group

the 100 and 1 000 nmol/L Dex groups had significantly decreased expression level of KIM-1 (0.19±0.01 and 0.18±0.02

0.25±0.02

0.05) and content of MDA (

0.05); the 10

100 and 1 000 nmol/L Dex groups obtained reduced levels of IL-6 and TNF-α (

0.05). ④ The level of TNF-α was obviously decreased in the 100 and 1 000 nmol/L Dex groups than the 1 and 10 nmol/L Dex groups (

0.05). ⑤ SOD activity was notably enhanced in the 1 000 nmol/L Dex group than the 0

0.1 and 10 nmol/L Dex groups (

0.05).

Conclusion

Dex shows protective effects on rat DCD donor kidneys in a dose-dependent manner

with the doses of 100 nmol/L and 1 000 nmol/L exerting the optimal effects

which may be due to its reducing apoptosis

inhibiting inflammatory response and anti-oxidative stress.

关键词

Keywords

references

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