芒果苷通过抑制炎症、肺泡化阻滞和肺微血管受损来减轻高氧诱导的新生小鼠肺损伤  

Mangiferin attenuates hyperoxia-induced lung injury in neonatal mice by inhibiting inflammatory response,alveolar arrest and pulmonary mi⁃crovascular injury

作　　者：胡军峰 聂颖 徐辉甫[1] HU Junfeng;NIE Ying;XU Huifu(Department of Pediatrics,Wuhan No.1 Hospital,Wuhan 430022,China.)

机构地区：[1]武汉市第一医院儿科,湖北武汉430022

出　　处：《中国病理生理杂志》2023年第6期1014-1020,共7页Chinese Journal of Pathophysiology

基　　金：2019年度武汉市卫生健康委员会医学科研项目(No.WX19C15)。

摘　　要：目的:研究芒果苷对高氧诱导的支气管肺发育不良(BPD)新生小鼠中肺损伤的治疗作用。方法:通过高氧暴露构建新生小鼠BPD模型,并通过ELISA法检测肺组织纤维蛋白的沉积水平以确定最佳芒果苷浓度。将新生小鼠随机分为对照组、芒果苷组、高氧组和高氧+芒果苷组,每组10只小鼠。芒果苷组和高氧+芒果苷组新生小鼠分别每天灌胃给予50 mg/kg芒果苷,连续14 d。第15天,新生小鼠称重,麻醉后处死,取肺脏并称重,并计算肺脏/体重比。通过HE染色评估各组肺组织的形态学改变情况;通过Ly-6B.2和CD68免疫组化标记法对各组肺组织中嗜中性粒细胞和巨噬细胞计数;通过ELISA法检测各组肺组织中炎症因子IL-1β、IL-6、TNF-α和IFN-γ含量变化;通过von Willebrand因子免疫荧光标记法对肺组织中微血管计数;通过Western blot检测各组肺组织中NF-κB信号相关蛋白表达情况。结果:芒果苷在0~50 mg/kg剂量范围内可呈剂量依赖地降低高氧导致的新生小鼠肺部纤维蛋白沉积,其中50 mg/kg剂量时效果最显著(P<0.01)。与高氧组比较,高氧+芒果苷组小鼠肺/体重比显著降低(P<0.01),肺组织中中性粒细胞和巨噬细胞数量以及炎症因子IL-1β、IL-6、TNF-α和IFN-γ的水平显著降低(P<0.05),辐射状肺泡数和微血管密度显著增加(P<0.05),p-NF-κB p65和p-IκBα的表达显著降低(P<0.01)。结论:芒果苷可通过改善新生小鼠肺泡结构异常、抑制炎症发生并促进血管生成,从而减轻高氧环境引起肺损伤。AIM:To investigate the therapeutic effect of mangiferin on lung injury in neonatal mice with hyperoxia-induced bronchopulmonary dysplasia(BPD).METHODS:The neonatal mice model of BPD was established by hyperoxia exposure,and the optimal dose of mangiferin was determined by the level of fibrin deposition in lung tissue measured by ELISA.Neonatal mice were divided into control group,mangiferin group,hyperoxia group and hyperoxia+mangiferin group,with 10 mice in each groups.Neonatal mice in mangiferin and hyperoxia+mangiferin groups were given 50 mg/kg mangiferin by intragastric administration daily for 14 consecutive days.On day 15,neonatal mice and their lungs were weighed and the lung/body weight ratio was calculated.The morphological changes of lung tissues were evaluated by HE staining.Neutrophils and macrophages in lung tissue were counted by immunohistochemical labeling Ly-6B.2 and CD68.The contents of IL-1β,IL-6,TNF-αand IFN-γin lung tissue were determined by ELISA.The microvessels were counted by von Willebrand factor(vWF)immunofluorescence labeling method.The expression levels of NF-κB signal-related proteins in lung tissue were detected by Western blot.RESULTS:Mangiferin reduced the pulmonary fibrin deposition induced by hyperoxia in a dose-dependent manner,with the most significant effect at 50 mg/kg(P<0.01).Compared with hyperoxia group,the lung/body weight ratio in hyperoxia+mangiferin group was significantly decreased(P<0.01),the number of neutrophils and macrophages and the levels of inflammatory cytokines IL-1β,IL-6,TNF-αand IFN-γwere significantly decreased(P<0.05),the number of radiative alveolar and the density of microvascular were significantly in‐creased(P<0.05),the expression levels of p-NF-κB p65 and p-IκBαwere significantly decreased(P<0.01).CON⁃CLUSION:Mangiferin protects against lung injury induced by hyperoxia though improving alveolar dysplasia,reducing inflammatory response and promoting angiogenesis in neonatal mice.

关 键 词：支气管肺发育不良 芒果苷 肺损伤 炎症 

分 类 号：R363.2[医药卫生—病理学] R562[医药卫生—基础医学] R931.71