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1.400042 重庆,陆军特色医学中心儿科
2.402260 重庆 江津,重庆大学附属江津医院儿科
[胡章雪, E-mail:huzx1@163.com HU Zhangxue, E-mail: huzx1@163.com
收稿:2023-06-15,
修回:2023-09-19,
纸质出版:2023-10-30
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李静, 唐佳, 李宛卫, 等. 维生素A缺乏加重胎粪吸入综合征大鼠肺损伤[J]. 陆军军医大学学报, 2023,45(20):2171-2178.
Jing LI, Jia TANG, Wanwei LI, et al. Vitamin A deficiency aggravates lung injury in rats with meconium aspiration syndrome[J]. Journal of Army Medical University, 2023, 45(20): 2171-2178.
李静, 唐佳, 李宛卫, 等. 维生素A缺乏加重胎粪吸入综合征大鼠肺损伤[J]. 陆军军医大学学报, 2023,45(20):2171-2178. DOI: 10.16016/j.2097-0927.202306071.
Jing LI, Jia TANG, Wanwei LI, et al. Vitamin A deficiency aggravates lung injury in rats with meconium aspiration syndrome[J]. Journal of Army Medical University, 2023, 45(20): 2171-2178. DOI: 10.16016/j.2097-0927.202306071.
目的
2
探讨维生素A(vitamin A,VA)缺乏在新生大鼠胎粪吸入综合征(meconium aspiration syndrome,MAS)中对肺损伤的影响。
方法
2
通过饲养VA缺乏及VA正常母鼠获得新生7 d VA缺乏SD大鼠(vitamin A deficiency,VAD)及VA正常新生SD大鼠(vitamin A normal,VAN)各25只,分别建立VA缺乏MAS模型(VAD组)及VA正常MAS模型(VAN组)。记录、对比、分析各组新生SD大鼠血气分析、肺组织湿/干质量比、HE染色评估肺组织损伤;ELISA检测肺组织SP-A蛋白、SP-C蛋白、IL-6、血管内皮生长因子(vascular endothelial growth factor,VEGF)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量;高效液相色谱检测肺组织β-丙氨酸及其他代谢组物指标。
结果
2
与VAN组比较,VAD组新生大鼠血气中pH值(
P
=0.003)、碱剩余(bas
e excess,BE)(
P
=0.019)显著降低,差异有统计学意义;VAD组血气中CO
2
分压(PCO
2
)(
P
=0.049)、肺组织的湿/干质量比(
P
=0.001)、IL-6(
P
=0.002)、VEGF(
P
=0.003)、TNF-α(
P
=0.019)显著增高,提示VAD组肺组织炎症反应更重。代谢组学分析表明:两组之间主要差异信号通路包括β-丙氨酸代谢通路、cGMP-PKG信号通路、嗅觉转导通路、神经活性配体-受体相互作用通路等,进一步通过液相色谱质谱技术检测并验证发现VAD组较VAN组中β-丙氨酸(
P
=0.000)显著上调。
结论
2
VA缺乏可通过上调MAS的炎症因子的表达加重肺损伤,这可能与VA缺乏后导致β-丙氨酸代谢通路改变有关。
Objective
2
To investigate the effect of vitamin A (VA) deficiency on lung injury in meconium aspiration syndrome (MAS) in newborn rats.
Methods
2
After pregnant rats were fed with normal and deficient VA diet
25 VA-deficient (VAD) and 25 VA-normal (VAN) neonatal SD rats (7 days old) were obtained
respectively. These rats were used to establish MAS mode. The results of blood gas analysis and wet/dry mass ratio of lung tissue were recorded
compared and analyzed in each group. HE staining was employed to evaluate lung tissue injury. The contents of SP-A protein
SP-C protein
IL-6
vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) in lung tissue were detected by ELISA. β-alanine and other metabolites in the lung tissue was measured with high performance liquid chromatography (HPLC).
Results
2
The pH value (
P
=0.003) and base excess (BE) (
P
=0.019) were significantly lower in the newborn rats from the VAD group than the VAN group. The VAD group had obviously higher partial pressure of carbon dioxide (PCO
2
) (
P
=0.049)
wet/dry mass ratio of lung tissue (
P
=0.001)
and contents of IL-6 (
P
=0.002)
VEGF (
P
=0.003) and TNF-α (
P
=0.019) than the VAD group
suggesting more serious lung inflammation in the VAD group. Furth
er metabolomic analysis showed that the major signaling pathways between VAD and VAN groups included β-alanine metabolism
cGMP-PKG signaling pathway
olfactory transduction pathway
and neural active ligand-receptor interaction pathway. The result of HPLC indicated that β-alanine was notably up-regulated in rats from the VAD group than the VAN group (
P
=0.000).
Conclusion
2
VAD can aggravate lung injury by up-regulating MAS inflammatory factors
which may be related to the changes in β-alanine metabolic pathways caused by VAD.
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