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外源性乳酸治疗创伤性脑损伤的消肿作用:一种生理和机制方法。

The Antiedematous Effect of Exogenous Lactate Therapy in Traumatic Brain Injury: A Physiological and Mechanistic Approach.

机构信息

Intensive Care Unit, Hospital Pasteur 2, Le Centre Hospitalier Universitaire de Nice, Nice, France.

UMR7275, Institut de Pharmacologie moléculaire et cellulaire, Valbonne, France.

出版信息

Neurocrit Care. 2021 Dec;35(3):747-755. doi: 10.1007/s12028-021-01219-y. Epub 2021 Apr 20.

DOI:10.1007/s12028-021-01219-y
PMID:33880700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8692279/
Abstract

BACKGROUND

Sodium lactate (SL) has been described as an efficient therapy in treating raised intracranial pressure (ICP). However, the precise mechanism by which SL reduces intracranial hypertension is not well defined. An antiedematous effect has been proposed but never demonstrated. In this context, the involvement of chloride channels, aquaporins, or K-Cl cotransporters has also been suggested, but these mechanisms have never been assessed when using SL.

METHODS

In a rat model of traumatic brain injury (TBI), we compared the effect of SL versus mannitol 20% on ICP, cerebral tissue oxygen pressure, and brain water content. We attempted to clarify the involvement of chloride channels in the antiedematous effects associated with lactate therapy in TBI.

RESULTS

An equimolar single bolus of SL and mannitol significantly reduced brain water content and ICP and improved cerebral tissue oxygen pressure 4 h after severe TBI. The effect of SL on brain water content was much longer than that of mannitol and persisted at 24 h post TBI. Western blot and immunofluorescence staining analyses performed 24 h after TBI revealed that SL infusion is associated with an upregulation of aquaporin 4 and K-Cl cotransporter 2.

CONCLUSIONS

SL is an effective therapy for treating brain edema after TBI. This study suggests, for the first time, the potential role of chloride channels in the antiedematous effect induced by exogenous SL.

摘要

背景

乳酸钠 (SL) 已被描述为治疗颅内压升高 (ICP) 的有效治疗方法。然而,SL 降低颅内高压的确切机制尚未明确定义。有人提出了抗水肿作用,但从未得到证实。在这种情况下,氯离子通道、水通道蛋白或 K-Cl 共转运体的参与也被提出,但在使用 SL 时从未评估过这些机制。

方法

在创伤性脑损伤 (TBI) 的大鼠模型中,我们比较了 SL 与 20%甘露醇对 ICP、脑组织氧压和脑水含量的影响。我们试图阐明氯离子通道在与乳酸盐治疗相关的 TBI 抗水肿作用中的参与。

结果

等摩尔单剂量 SL 和甘露醇可显著降低 TBI 后 4 小时的脑水含量和 ICP,并改善脑组织氧压。SL 对脑水含量的作用比甘露醇长得多,在 TBI 后 24 小时仍持续存在。TBI 后 24 小时进行的 Western blot 和免疫荧光染色分析显示,SL 输注与水通道蛋白 4 和 K-Cl 共转运蛋白 2 的上调有关。

结论

SL 是治疗 TBI 后脑水肿的有效治疗方法。本研究首次提示外源性 SL 诱导的抗水肿作用中氯离子通道的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/d7e54a88ae5a/12028_2021_1219_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/f5c2e30fd9db/12028_2021_1219_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/99ff4db70c5c/12028_2021_1219_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/0d996715a0bd/12028_2021_1219_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/d7e54a88ae5a/12028_2021_1219_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/f5c2e30fd9db/12028_2021_1219_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/99ff4db70c5c/12028_2021_1219_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/0d996715a0bd/12028_2021_1219_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/8692279/d7e54a88ae5a/12028_2021_1219_Fig4_HTML.jpg

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