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阻断 CD40/CD40L 复合物可保护小鼠免受 ALI 诱导的胰腺降解。

Inhibition of the CD40/CD40L complex protects mice against ALI-induced pancreas degradation.

机构信息

Université de Lyon, GIMAP-EA3064, Saint-Etienne, France.

Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Etienne, France.

出版信息

Transfusion. 2019 Mar;59(3):1090-1101. doi: 10.1111/trf.15206. Epub 2019 Feb 19.

DOI:10.1111/trf.15206
PMID:30784079
Abstract

BACKGROUND

Acute lung injury (ALI) is a severe complication of transfusion. In a previous study, we saw that inhibition of the CD40/CD40L complex allowed restoration of ALI lesions in an experimental mouse model.

OBJECTIVES

This study focused on pancreas-associated injury development during experimental ALI pathogenesis and its limitation through CD40/CD40L complex inhibition.

MATERIALS AND METHODS

An ALI mouse model was established through intraperitoneal lipopolysaccharide and intravenous anti-major histocompatibility complex class I monoclonal antibody injection. Preemption of lesions was achieved with intravenous injection of neutralizing anti-CD40L monoclonal antibody 30 minutes before the trigger, that is, anti-major histocompatibility complex class I monoclonal antibody administration. Histology and immunoassay analyses were used to evaluate pancreatic lesions.

RESULTS

ALI development induced significant degradation of the lungs and pancreas and was associated with pancreatic lesions. Different scores were established showing more severe injury to the pancreas in ALI conditions; however, injury was significantly reduced through CD40/CD40L complex inhibition.

CONCLUSION

This study supports the idea that several organs are exposed during ALI development, and particularly when such experimental ALI aims at mimicking transfusion-associated ALI; nevertheless, preventive treatment inhibiting CD40/CD40L (sCD40L) complex formation provides protection from lung disease as well as disease of other organs.

摘要

背景

急性肺损伤(ALI)是输血的严重并发症。在之前的研究中,我们发现抑制 CD40/CD40L 复合物可以恢复实验小鼠模型中的 ALI 损伤。

目的

本研究专注于实验性 ALI 发病过程中胰腺相关损伤的发展及其通过 CD40/CD40L 复合物抑制的局限性。

材料和方法

通过腹腔内注射脂多糖和静脉注射抗主要组织相容性复合体 I 单克隆抗体建立 ALI 小鼠模型。通过在触发前 30 分钟静脉注射中和抗 CD40L 单克隆抗体来预先阻止病变,即抗主要组织相容性复合体 I 单克隆抗体给药。采用组织学和免疫测定分析评估胰腺病变。

结果

ALI 的发展导致肺部和胰腺明显退化,并伴有胰腺损伤。建立了不同的评分,显示在 ALI 条件下胰腺损伤更严重;然而,通过抑制 CD40/CD40L 复合物,损伤显著减少。

结论

本研究支持这样一种观点,即在 ALI 发展过程中暴露了多个器官,特别是当这种实验性 ALI 旨在模拟输血相关的 ALI 时;然而,抑制 CD40/CD40L(sCD40L)复合物形成的预防性治疗不仅可以预防肺部疾病,还可以预防其他器官的疾病。

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