维生素A缺乏调节肺泡巨噬细胞M1极化在新生大鼠ARDS中的作用及其机制

曾毅文; 龚放

doi:10.11855/j.issn.0577-7402.2420.2023.0619

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维生素A缺乏调节肺泡巨噬细胞M1极化在新生大鼠ARDS中的作用及其机制

基础研究 | 更新时间：2023-11-09

- 维生素A缺乏调节肺泡巨噬细胞M1极化在新生大鼠ARDS中的作用及其机制
- Effect and mechanism of vitamin A deficiency in regulating M1 polarization of alveolar macrophage in neonatal rats with ARDS
- 解放军医学杂志 2023年48卷第10期页码：1144-1152
- 作者机构：
  
  1.重庆医科大学附属永川医院儿科，重庆　402160
- 作者简介：
  
  曾毅文，硕士研究生，副主任医师，主要从事新生儿疾病方面的研究
  龚放，E-mail：gf607812@163.com
- 基金信息：
  
  重庆市教委项目(KJQN201900420)
- DOI：10.11855/j.issn.0577-7402.2420.2023.0619
  中图分类号：
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曾毅文, 龚放. 维生素A缺乏调节肺泡巨噬细胞M1极化在新生大鼠ARDS中的作用及其机制[J]. 解放军医学杂志, 2023, 48(10): 1144-1152.

Zeng Yi-Wen,Gong Fang.Effect and mechanism of vitamin A deficiency in regulating M1 polarization of alveolar macrophage in neonatal rats with ARDS[J].Medical Journal of Chinese People′s Liberation Army,2023,48(10):1144-1152.
曾毅文, 龚放. 维生素A缺乏调节肺泡巨噬细胞M1极化在新生大鼠ARDS中的作用及其机制[J]. 解放军医学杂志, 2023, 48(10): 1144-1152. DOI： 10.11855/j.issn.0577-7402.2420.2023.0619.

Zeng Yi-Wen,Gong Fang.Effect and mechanism of vitamin A deficiency in regulating M1 polarization of alveolar macrophage in neonatal rats with ARDS[J].Medical Journal of Chinese People′s Liberation Army,2023,48(10):1144-1152. DOI： 10.11855/j.issn.0577-7402.2420.2023.0619.

摘要

目的,2,探讨维生素A缺乏(VAD)调节肺泡巨噬细胞极化在新生大鼠急性呼吸窘迫综合征(ARDS)中的作用及其机制。,方法,2,将60只新生SD大鼠分为维生素A正常对照组(VAN ctrl组，,n,=10)、维生素A正常组(VAN组，,n,=10)、维生素A缺乏对照组(VAD ctrl组，,n,=10)、维生素A缺乏组(VAD组，,n,=10)、维生素A挽救对照组(VADR ctrl组，,n,=10)及维生素A挽救组 (VADR组，,n,=10)，其中，VADR ctrl及VADR组SD大鼠于生后第2天一次性给予腹腔注射25 µg VA。6组新生大鼠分别予以脂多糖(LPS)建立ARDS新生大鼠模型并收集血清及肺组织标本。记录建模前各组新生大鼠的体重，采用May-Grunwald-Giemsa染色法检测肺泡灌洗液(BALF)中主要细胞数量，HE染色观察肺组织病理损伤情况，免疫荧光染色评估肺泡巨噬细胞极化情况，qRT-PCR、ELISA检测肺泡巨噬细胞极化下游标志物诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10、精氨酸酶1(Arg-1)等炎性因子的表达情况，比色法检测肺组织氧化应激标志物超氧化物歧化酶(SOD)、丙二醛(MDA)含量，TUNEL检测细胞凋亡情况。,结果,2,与VAN组新生大鼠比较，VAD组新生大鼠体重较轻、体格偏小、毛发稀疏，而VADR组新生大鼠体重、一般情况无明显变化；与VAD组比较，VADR组新生大鼠体重增加，毛发光亮。与VAN组比较，VAD组ARDS新生大鼠肺部损伤加重，BALF中主要细胞数量增加、肺泡巨噬细胞M1极化激活(,P,<,0.05)，M1极化标志物iNOS、IL-6、TNF-α、CD86表达水平明显升高(,P,<,0.05)，氧化应激标志物MDA含量增多(,P,<,0.05)，细胞凋亡增加(,P,<,0.05)，SOD活性降低(,P,<,0.05)，而IL-10、Arg-1水平差异无统计学意义(,P,>,0.05)；与VAN组相比，VADR组新生大鼠巨噬细胞M1极化及TNF-α、IL-6、SOD、MDA、IL-10、Arg-1水平等差异均无统计学意义(,P,>,0.05)；与VAD组比较，VADR组ARDS新生大鼠肺部损伤明显减轻，肺泡巨噬细胞数量及肺泡巨噬细胞M1极化减少(,P,<,0.05)，且M1极化标志物iNOS、IL-6、TNF-α、CD86表达水平降低(,P,<,0.05)，氧化应激标志物MDA含量及细胞凋亡减少(,P,<,0.05)，SOD活性增加(,P,<,0.05)。,结论,2,VAD可通过调节肺泡巨噬细胞M1极化，上调M1极化下游炎症标志物表达，增加肺部氧化应激及细胞凋亡，从而加重新生大鼠ARDS的肺部损伤。

Abstract

Objective,2,To investigate the effect and its mechanism of vitamin A (VA) deficiency (VAD) on regulating alveolar macrophage polarization in neonatal rats with acute respiratory distress syndrome (ARDS).,Methods,2,Sixty neonatal SD rats were divided into vitamin A normal control group (VAN ctrl group,n,=10), normal vitamin A group (VAN group,n,=10), vitamin A deficiency control group (VAD ctrl group,n,=10), vitamin A deficiency group (VAD group,n,=10), vitamin A rescue control group (VADR ctrl group,n,=10) and vitamin A rescue group (VADR group,n,=10). The VADR ctrl and VADR groups were injected with,25 µg VA at the second day after birth. All the neonatal rats were given lipopolysaccharide (LPS) to establish the neonatal rat model of ARDS, and serum and lung tissue samples were collected. The weight of newborn rats in each group was recorded before modeling, the May-Grunwald-Giemsa staining was performed to observe the number of main cells in bronchoalveolar lavage fluid (BALF), and HE staining was used to detect the pathological damage of lung tissue. The polarization of alveolar macrophages was evaluated by immunofluorescence. qRT-PCR and ELISA were performed to detected the expression of downstream markers of the polarization of alveolar macrophages inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10 and arginase-1 (Arg-1). The content of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were calculated by colorimetric method, and cell apoptosis was detected by TUNEL.,Results,2,Compared with the neonatal rats in VAN group, the neonatal rats in VAD group had lower body weight, small physique, and sparse hair, while the body weight and general condition of the newborn rats in the VADR group did not change significantly. Compared with the VAD group, the neonatal rats in VADR group gained weight and shiny hair. Compared with VAN group, the lung damage of ARDS neonatal rats in VAD group was aggravated, the number of major cells in BALF increased, the M1 polarization of alveolar macrophages activated (,P,<,0.05), the expression levels of M1 polarization markers iNOS, IL-6, TNF-α and CD86 increased significantly (,P,<,0.05), the content of oxidative stress marker MDA and cell apoptosis increased (,P,<,0.05), SOD activity decreased (,P,<,0.05), while the levels of IL-10 and Arg-1 were not statistically significant (,P,>,0.05); Compared with VAN group, there were no significant differences in macrophage M1 polarization, TNF-α, IL-6, SOD, MDA, IL-10 and Arg-1 in newborn rats in VADR group (,P,>,0.05). Compared with VAD group, the lung damage of ARDS neonatal rats in VADR group was significantly reduced, the number of alveolar macrophages and the polarization of alveolar macrophages M1 decreased (,P,<,0.05), the expression levels of M1 polarization markers iNOS, IL-6, TNF-α and CD86 decreased (,P,<,0.05), the content of the oxidative stress marker MDA and cell apoptosis decreased (,P,<,0.05), and the SOD activity enhanced (,P,<,0.05).,Conclusion,2,VAD could regulate the M1 polarization of alveolar macrophages, up-regulated the expression of inflammatory markers downstream of M1 polarization, increased pulmonary oxidative stress and apoptosis, and aggravated ARDS in neonatal rats.

关键词

维生素A缺乏新生儿急性呼吸窘迫综合征肺泡巨噬细胞M1极化氧化应激炎性因子

Keywords

vitamin A deficiencynewbornacute respiratory distress syndromealveolar macrophage M1 polarizationoxidative stressinflammatory factors

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