供体吸入雾化右美托咪定可减轻大鼠肺移植中的缺血再灌注损伤。

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacology Pub Date : 2024-01-01 Epub Date: 2024-05-28 DOI:10.1159/000539528
Jing Wang, Jiaojiao Sun, Huizhi Yu, Chunlan Hu, Jinbo Wu, Chunxiao Hu
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引用次数: 0

摘要

导言:肺移植术后发生肺缺血再灌注损伤(LIRI),50%以上的病例会导致原发性移植物功能障碍(PGD),严重影响受者的预后。目前,供体肺保护是提高肺移植受者移植物存活率的研究重点。右美托咪定(Dex)是临床上广泛使用的全身麻醉辅助药物,可减轻肺、肝、心、肾和脑的缺血再灌注损伤。然而,静脉注射地塞米松会对心血管系统造成负面影响。雾化吸入地塞米松可直接作用于肺泡组织,通过减少药物摄入缓解其对心血管的抑制作用。本研究旨在探讨供体雾化吸入Dex对大鼠肺移植后LIRI的影响:我们将雄性 Sprague-Dawley 大鼠随机分配到供体组,术前 15 分钟吸入雾化 Dex 或生理盐水。供体肺在每次单肺移植前冷藏 8 小时。移植肺再灌注 2 小时后,收集血清和移植肺组织。测量肺组织的干湿重量比,检测动脉血气,评估组织病理学变化、氧化应激、炎症反应和细胞凋亡:结果:移植前通过供体肺吸入地塞米松可减轻移植肺的损伤,提高肺组织中丙二醛和髓过氧化物酶的水平,降低超氧化物歧化酶和谷胱甘肽的水平。此外,供体肺雾化吸入 Dex 可抑制 LIRI 诱导的肿瘤坏死因子-α、白细胞介素-6 和诱导型一氧化氮合酶的表达,还可抑制核因子-kappa B 的磷酸化。雾化吸入 Dex 可抑制 LIRI 引起的 Bax 上调、Bcl-2 下调和 caspase-3 裂解增加,从而降低移植肺组织的细胞凋亡率:吸入雾化 Dex 是一种潜在的供肺保护策略,可用于降低肺移植后的 LIRI,并可能有助于改善肺移植受者 PGD 的发生率和预后。
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Donor Inhalation of Nebulized Dexmedetomidine Alleviates Ischemia-Reperfusion Injury in Rat Lung Transplantation.

Introduction: The occurrence of lung ischemia-reperfusion injury (LIRI) after lung transplantation results in primary graft dysfunction (PGD) in more than 50% of cases, which seriously affects the prognosis of recipients. Currently, donor lung protection is the focus of research on improving graft survival in lung transplant recipients. Dexmedetomidine (Dex) is a widely used general anesthesia adjuvant in clinical practice to alleviate ischemia-reperfusion injury in the lungs, liver, heart, kidneys, and brain. However, intravenous infusion of Dex can cause negative effects on the cardiovascular system. Inhaling nebulized Dex can directly act on the alveolar tissue and alleviate its cardiovascular inhibitory effect by reducing drug intake. This study aimed to investigate the effect of donor nebulized Dex inhalation on LIRI after lung transplantation in rats.

Methods: We randomly divided the male Sprague-Dawley rats into donor rats and recipient rats, and allowed the donor rats to inhale nebulized Dex or physiological saline 15 min before surgery. The donor lung was refrigerated for 8 h before each single-lung transplant. After 2 h of reperfusion of the transplanted lung, serum and transplanted lung tissue were collected. The wet-to-dry weight ratio of the lung tissue was measured, arterial blood gas was detected, and histopathology changes, oxidative stress, inflammatory reactions, and apoptosis were evaluated.

Results: Pretransplant inhalation of Dex through the donor's lung reduced the injury of the transplanted lung, increased the levels of malondialdehyde and myeloperoxidase, and decreased the levels of superoxide dismutase and glutathione in the lung tissue. Moreover, nebulized Dex inhalation of the donor lung inhibited LIRI-induced tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase expression and also suppressed nuclear factor kappa B phosphorylation. Nebulized Dex inhalation reduced the rate of cell apoptosis in the transplanted lung tissue by inhibiting the upregulation of Bax, downregulation of Bcl-2, and increase in caspase-3 lysis caused by LIRI.

Conclusion: Inhalation of atomized Dex is a potential donor lung protection strategy, which can be used to reduce LIRI after lung transplantation and may be helpful to improve the occurrence of PGD and prognosis of lung transplant recipients.

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来源期刊
Pharmacology
Pharmacology 医学-药学
CiteScore
5.60
自引率
0.00%
发文量
52
审稿时长
6-12 weeks
期刊介绍: ''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.
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