啮齿动物心肺旁路模型显示全身炎症和神经标记物变化

IF 1.8 3区医学 Q2 SURGERY

Journal of Surgical Research Pub Date : 2024-11-01 DOI:10.1016/j.jss.2024.09.041

Aimee Zhang MD , Nathan S. Haywood MD , Dustin T. Money RRT-ACCS , Matthew R. Byler MD, MBA , Hari P. Osuru PhD , Navya Atluri PhD , Victor E. Laubach PhD , J. Hunter Mehaffey MD, MSc , Jennifer R. Charlton MD , Nadia Lunardi MD, PhD , Irving L. Kron MD , Nicholas R. Teman MD

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引用次数: 0

摘要

导言：心肺旁路术（CPB）引起的生理失调可导致术后谵妄等并发症。我们的目的是验证一种显示全身炎症反应的 CPB 啮齿类存活模型，并推测这将导致 CPB 术后谵妄：方法：成年 Sprague-Dawley 大鼠被随机分为三组：1）假外周手术插管组；2）CPB 后急性期收获组；或 3）CPB 后 24 小时存活组。CPB持续60分钟，然后拔管并从机械通气中断气。对各组的生理和生化终点进行比较。使用定量 RT-PCR 面板对海马组织进行基因表达分析，并通过 Western 印迹确认蛋白质表达水平：结果：16 只动物接受了插管手术，并在不需要输血或使用肌注的情况下成功拔管，其中有一只动物因手术相关死亡。与假手术相比，CPB 1 小时后血清急性期促炎趋化因子细胞因子诱导的中性粒细胞趋化吸引子 1、细胞因子诱导的中性粒细胞趋化吸引子 3、分叉碱和脂多糖诱导的 CXC 趋化因子以及白细胞介素 (IL)-10 均有所增加（P 结论：该研究验证了 CPB 模型的有效性：这项研究验证了一种能捕捉到由此引起的全身炎症反应的 CPB 模型，并确定了可能与脑损伤有关的不同表达蛋白。调节 CPB 引起的炎症反应可能是减轻 CPB 后谵妄的一个很有前景的治疗靶点，而且这种存活的 CPB 大鼠模型手术损耗低，因此可以对 CPB 和潜在治疗干预的短期和长期影响进行更全面的评估。

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Rodent Model of Cardiopulmonary Bypass Demonstrates Systemic Inflammation and NeuroMarker Changes

Introduction

The physiologic derangements imposed by cardiopulmonary bypass (CPB) can result in complications such as postoperative delirium. We aim to validate a rodent survival model of CPB demonstrating a systemic inflammatory response and hypothesize that this contributes to post-CPB delirium.

Methods

Adult Sprague–Dawley rats were randomized to three groups: 1) Sham peripheral surgical cannulation, 2) CPB followed by acute phase harvest, or 3) CPB followed by 24-h survival. CPB was carried out for 60 min before decannulation and weaning from mechanical ventilation. Physiological and biochemical endpoints were compared between groups. Gene expression analysis of hippocampal tissue was performed using quantitative RT-PCR panels and protein expression levels were confirmed with Western blot.

Results

Sixteen animals underwent cannulation and were successfully decannulated without transfusion requirement or inotrope use with one procedure-related mortality. Serum acute phase proinflammatory chemokines cytokine-induced neutrophil chemoattractant 1, cytokine-induced neutrophil chemoattractant 3, fractalkine, and lipopolysaccharide-induced CXC chemokine as well as interleukin (IL)-10 were increased 1 h following CPB compared to sham (P < 0.05). Significant changes in hippocampal expression of biomarkers apolipoprotein 1, vascular epithelial growth factor A, and synapsin 1 were demonstrated following CPB.

Conclusions

This study validated a model of CPB that captures the resultant systemic inflammatory response, and identified differentially expressed proteins that may be associated with brain injury. Modulation of the CPB-induced inflammatory response may be a promising therapeutic target to attenuate post-CPB delirium, and this survival rat model of CPB with low surgical attrition will allow for more comprehensive evaluations of the short- and long-term effects of both CPB and potential therapeutic interventions.

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来源期刊

Journal of Surgical Research 医学-外科

CiteScore

3.90

自引率

4.50%

发文量

627

审稿时长

138 days

期刊介绍： The Journal of Surgical Research: Clinical and Laboratory Investigation publishes original articles concerned with clinical and laboratory investigations relevant to surgical practice and teaching. The journal emphasizes reports of clinical investigations or fundamental research bearing directly on surgical management that will be of general interest to a broad range of surgeons and surgical researchers. The articles presented need not have been the products of surgeons or of surgical laboratories. The Journal of Surgical Research also features review articles and special articles relating to educational, research, or social issues of interest to the academic surgical community.