关键词: 17β-estradiol brain death females lung methylprednisolone

Mesh : Animals Female Estradiol / pharmacology Methylprednisolone / pharmacology Rats Rats, Wistar Brain Death Pneumonia / drug therapy metabolism Cytokines / metabolism Lung / drug effects pathology metabolism immunology Disease Models, Animal Anti-Inflammatory Agents / pharmacology therapeutic use

来  源:   DOI:10.3389/fimmu.2024.1375943   PDF(Pubmed)

Abstract:
UNASSIGNED: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats.
UNASSIGNED: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction).
UNASSIGNED: Hemodynamics, systemic and local quantification of IL-6, IL-1β, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue.
UNASSIGNED: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.
摘要:
已知脑死亡(BD)通过引起血液动力学而损害移植物质量,新陈代谢,和荷尔蒙的变化。BD后女性性激素的突然减少与肺部炎症增加有关。在调节BD诱导的炎症反应中,单独使用皮质类固醇和雌二醇都表现出积极的结果。然而,研究表明,对于女性,雌激素和皮质激素的存在对于确保足够的免疫反应是必要的。在这个意义上,本研究旨在探讨甲基强的松龙(MP)和雌二醇(E2)的联合如何调节雌性大鼠BD引发的肺部炎症。
雌性Wistar大鼠(8周)分为四组:假(接受外科手术的动物,不诱导BD),BD(提交给BD的动物),MP/E2(在BD诱导后3h接受MP和E2处理的接受BD的动物)和MP(在BD诱导后3h接受MP处理的接受BD的动物)。
血流动力学,IL-6,IL-1β的全身和局部定量,VEGF,和TNF-α,白细胞浸润到肺实质和气道,和粘附分子表达进行分析。治疗后,MP/E2关联能够将平均动脉压恢复至接近假手术动物的水平(p<0.05)。BD增加了白细胞向气道的浸润,MP/E2能够减少细胞数量(p=0.0139)。此外,相关治疗通过降低肺组织中VEGF的表达(p=0.0616)和维持eNOS水平(p=0.004)来调节血管系统。
本研究中提供的数据表明,通过在供体的血液动力学管理中呈现积极作用,皮质激素和雌二醇之间的关联可以代表女性BD供体肺部炎症的更好治疗策略。以及通过减少浸润到气道的白细胞和短期和长期的炎症标志物的释放。
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