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右美托咪定减轻静脉-动脉体外膜肺氧合大鼠模型中的急性肾损伤。

Dexmedetomidine alleviates acute kidney injury in a rat model of veno-arterial extracorporeal membrane oxygenation.

作者信息

Yu Min, Wei Shilin, Shen Xueyang, Ying Junjie, Mu Dezhi, Wu Xiangyang, Li Yongnan

机构信息

Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.

Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.

出版信息

Intensive Care Med Exp. 2025 Jan 30;13(1):12. doi: 10.1186/s40635-025-00720-4.

DOI:10.1186/s40635-025-00720-4
PMID:39884997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11782784/
Abstract

BACKGROUND

Although extracorporeal membrane oxygenation (ECMO) is an effective technique for life support, the incidence of acute kidney injury (AKI) during ECMO support remains high. Dexmedetomidine (DEX), which has been widely used for sedation during ECMO, possesses several properties that help reduce the occurrence of AKI. This study aimed to investigate the protective effect of DEX on kidney function during ECMO.

METHODS

A total of 18 male Sprague-Dawley (SD) rats were randomly divided into three groups: Sham, ECMO, and ECMO + DEX groups. ECMO was established through the right jugular vein for venous drainage and right femoral artery for arterial infusion and lasts for four hours. Hematoxylin and eosin staining was used to evaluate the kidney Paller score for the rats in each group. Enzyme-linked immunosorbent assay was used to measure the levels of kidney injury biomarkers and cytokines in the serum. Reagent kits were used to measure the blood urea nitrogen (BUN) and creatinine (Cr) levels, which helped determine kidney function. Immunohistochemical staining was used to evaluate neutrophil infiltration in the kidney.

RESULTS

The pathological Paller score was substantially lower in the ECMO + DEX group. The levels of Kidney Injury Molecule-1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) were also significantly reduced. The kidney functionality, as indicated by BUN and Cr, was significantly improved compared with the ECMO group. The levels of cytokines IL-6, IL-1β, and TNF-α, were also significantly decreased in the ECMO + DEX group.

CONCLUSION

This study demonstrated that dexmedetomidine could reduce inflammatory response and alleviate AKI during ECMO support.

摘要

背景

尽管体外膜肺氧合(ECMO)是一种有效的生命支持技术,但在ECMO支持期间急性肾损伤(AKI)的发生率仍然很高。右美托咪定(DEX)已广泛用于ECMO期间的镇静,它具有多种有助于减少AKI发生的特性。本研究旨在探讨DEX对ECMO期间肾功能的保护作用。

方法

总共18只雄性Sprague-Dawley(SD)大鼠随机分为三组:假手术组、ECMO组和ECMO+DEX组。通过右颈静脉进行静脉引流,右股动脉进行动脉灌注建立ECMO,持续4小时。采用苏木精-伊红染色评估每组大鼠的肾脏Paller评分。采用酶联免疫吸附测定法测量血清中肾损伤生物标志物和细胞因子的水平。使用试剂盒测量血尿素氮(BUN)和肌酐(Cr)水平,以帮助确定肾功能。采用免疫组织化学染色评估肾脏中的中性粒细胞浸润情况。

结果

ECMO+DEX组的病理Paller评分显著降低。肾损伤分子-1(KIM-1)和N-乙酰-β-D-氨基葡萄糖苷酶(NAG)的水平也显著降低。与ECMO组相比,BUN和Cr所表明的肾功能显著改善。ECMO+DEX组中细胞因子IL-6、IL-1β和TNF-α的水平也显著降低。

结论

本研究表明,右美托咪定可减轻ECMO支持期间的炎症反应并缓解AKI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/98f2b53f46fa/40635_2025_720_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/7e0ac7ebb013/40635_2025_720_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/645b586888c9/40635_2025_720_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/8b8b061d343f/40635_2025_720_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/98f2b53f46fa/40635_2025_720_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/7e0ac7ebb013/40635_2025_720_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/645b586888c9/40635_2025_720_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/30b7e9682e5d/40635_2025_720_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/41e72929b319/40635_2025_720_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/8b8b061d343f/40635_2025_720_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60c/11782784/98f2b53f46fa/40635_2025_720_Fig6_HTML.jpg

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Immunosuppressive therapies attenuate paraquat-induced renal dysfunction by suppressing inflammatory responses and lipid peroxidation.免疫抑制疗法通过抑制炎症反应和脂质过氧化来减轻百草枯引起的肾功能障碍。
Free Radic Biol Med. 2022 Oct;191:249-260. doi: 10.1016/j.freeradbiomed.2022.08.031. Epub 2022 Aug 27.
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Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 α2-AR.
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Front Pharmacol. 2022 Jun 14;13:782466. doi: 10.3389/fphar.2022.782466. eCollection 2022.
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Veno-Venous Extracorporeal Membrane Oxygenation in Minipigs as a Robust Tool to Model Acute Kidney Injury: Technical Notes and Characteristics.小型猪静脉-静脉体外膜肺氧合作为模拟急性肾损伤的可靠工具:技术要点与特征
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