右美托咪定对急性肾损伤继发肺损伤的修复功用

黎洁钰; 秦志刚; 薛正威; 刘祥凤; 江玲; 李鹏; 顾健腾

doi:10.16016/j.2097-0927.202310070

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右美托咪定对急性肾损伤继发肺损伤的修复功用

基础医学 | 更新时间：2026-01-09

- 右美托咪定对急性肾损伤继发肺损伤的修复功用
- Reparative role of dexmedetomidine in lung injury secondary to acute kidney injury
- 陆军军医大学学报 2024年46卷第1期页码：66-72
- 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：
  
  [顾健腾，E-mail：gjt1976@163.com GU Jianteng, E-mail: gjt1976@163.com
- 基金信息：
  
  重庆英才项目基金(CQYC20220303588);陆军军医大学人才基金(XZ-2019-505-028)
- DOI：10.16016/j.2097-0927.202310070
  中图分类号： R563;R692;R971.93
- 收稿：2023-10-18，
  
  修回：2023-12-08，
  
  纸质出版：2024-01-15
- 稿件说明：
移动端阅览
黎洁钰, 秦志刚, 薛正威, 等. 右美托咪定对急性肾损伤继发肺损伤的修复功用[J]. 陆军军医大学学报, 2024,46(1):66-72.

Jieyu LI, Zhigang QIN, Zhengwei XUE, et al. Reparative role of dexmedetomidine in lung injury secondary to acute kidney injury[J]. Journal of Army Medical University, 2024, 46(1): 66-72.
黎洁钰, 秦志刚, 薛正威, 等. 右美托咪定对急性肾损伤继发肺损伤的修复功用[J]. 陆军军医大学学报, 2024,46(1):66-72. DOI： 10.16016/j.2097-0927.202310070.

Jieyu LI, Zhigang QIN, Zhengwei XUE, et al. Reparative role of dexmedetomidine in lung injury secondary to acute kidney injury[J]. Journal of Army Medical University, 2024, 46(1): 66-72. DOI： 10.16016/j.2097-0927.202310070.

摘要

目的

探讨右美托咪定(Dexmedetomidine，Dex)对急性肾损伤(acute kidney injury，AKI)继发肺损伤的修复功用。

方法

将75只6~8周龄健康SPF级雄性C57BL/6J小鼠(体质量20~22 g)随机分为：假手术(Sham)组，常规行开腹关腹手术；肾缺血再灌注(RIR)组，双侧肾蒂夹闭50 min后再灌注；Dex预处理(Dex + RIR)组，双侧肾蒂夹闭前15 min经腹腔注射Dex(25 μg/kg)。各组于造模后24、48、72、96、120 h(

=5)，收集肺组织、肺泡灌洗液(bronchoalveolar lavage fluid，BALF)、颈动脉血。观察并比较各组不同时间点肺组织损伤程度及修复情况、动脉血氧分压(PaO

)、肺泡灌洗液转化生长因子β1(transforming growth factor β1

TGF-β1)和结缔组织生长因子(connective tissue growth factor

CTGF)含量。反转录实时定量聚合酶链式反应(quantitative real-time RT-PCR，RT-qPCR)检测肺组织白细胞介素-6(

IL-6

)、肺表面活性蛋白C(surfactant protein C，

SP-C

)转录水平。

结果

与Sham组比较，AKI后48 h内，RIR组和Dex+RIR组肺损伤评分升高、PaO

降低，但Dex+RIR组肺损伤评分及PaO

水平均优于RIR组；AKI后96 h内RIR组肺损伤评分维持高水平，PaO

维持低水平，而Dex+RIR组肺损伤评分和PaO

于48 h后出现持续好转。AKI后RIR组肺泡灌洗液TGF-β1和CTGF以及肺组织

IL-6

转录水平呈现出由高水平向低水平变化的趋势，但均显著高于Sham组(

＜0.05)，Dex干预使24~120 h时间点TGF-β1显著降低(

0.01)，24~72 h

IL-6

转录水平显著降低(

0.05)，而CTGF呈上升趋势并于48~96 h维持较高水平；AKI后RIR组

SP-C

转录水平在24 h显著上调(与Sham组比较，

0.001)，48~120 h大幅下降至低水平(与RIR组24 h比较，

0.05)，而Dex可改善此种AKI所致的

SP-C

转录抑制现象。

结论

Dex可改善急性肾损伤继发肺损伤后肺换气功能，并将肺损伤修复时间窗从96~120 h提前至48~72 h。

Abstract

Objective

To investigate the reparative role of dexmedetomidine (Dex) in lung injury secondary to acute kidney injury (AKI).

Methods

A total of 75 healthy SPF male C57BL/6J mice (6-8 weeks old

weighing 20-22 g) were randomly divided into Sham group (standard laparotomy)

renal ischemia reperfusion group (RIR

clamping of bilateral renal pedicles for 50 min followed by repe

rfusion)

and Dex pretreatment group (Dex+RIR

intraperitoneal injection of 25 μg/kg Dex 15 min before bilateral renal pedicle clamping). Lung tissues

bronchoalveolar lavage fluid (BALF)

and carotid arterial blood samples were collected from 5 mice in each group at 24

and 120 h after modeling. Lung injury and repair

arterial blood partial pressure of oxygen (PaO

)

and BALF contents of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were observed and detected for comparison in the groups at different time points. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the transcript levels of interleukin-6(

IL-6

) and lung surfactant protein C (

SP-C

Results

Within 48 h after AKI

lung injury score was increased and PaO

was decreased in the RIR group and Dex+RIR group than the Sham group

but Dex pretreatment reversed the lung injury score and PaO

level when compared with the RIR group. The lung injury score was still in a high level and PaO

stayed low in the RIR group within 96 h after AKI

whereas the 2 indicators in the Dex+RIR group showed a sustained improvement in 48 h after injury. After AKI

the BALF contents of TGF-β1 and CTGF and mRNA level of

IL-6

in lung tissue showed a decreasing trend from high level to low level in the RIR group

but all of them were significantly higher than those in the Sham group (

0.05)

while Dex intervention resulted in an obvious decrease of TGF-β1 at 24-120 h (

0.01) and a notable reduction of

IL-6

mRNA level at 24-72 h (

0.05)

whereas a raising trend and maintenance of high level in CTGF at 48-96 h. After AKI

the mRNA level of

SP-C

in the RIR group were up-regulated at 24 h (

0.001

when compared to the Sham group) and then dimin

ished to a low level at 48-120 h (

0.05

when compared to the RIR group at 24 h)

however Dex pretreatment could alleviate the transcriptional repression of

SP-C

caused by AKI.

Conclusion

Dex can ameliorate pulmonary ventilation after lung injury secondary to AKI

and then advance the time for lung repair from 96-120 h to 48-72 h.

关键词

Keywords

references

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