脐带间充质干细胞对高氧致新生大鼠肺损伤的保护作用

Protective effect of umbilical cord-derived mesenchymal stem cells on lung injury induced by hyperoxia in rats

目的探讨脐带间充质干细胞(UC-MSCs)对高氧致新生大鼠肺损伤的保护作用及其分子机制。方法将出生24 h内的96只新生Sprague-Dawley大鼠随机分为空气对照组、UC-MSCs对照组、支气管肺炎发育不良(BPD)模型组、UC-MSCs治疗组,每组24只。比较各组大鼠体重、支气管肺泡灌洗液(BALF)中总蛋白、总细胞计数、中性粒细胞计数及外周血白细胞介素(IL)-1β、IL-8、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)指标水平变化,并对各组肺组织原纤维蛋白-1(FBN1)、FBN2、Fibulin mRNA表达水平进行比较。结果UC-MSCs治疗组大鼠第14、21天体重与BPD模型组比较,差异均有统计学意义(P<0.05)。BPD模型组、UC-MSCs治疗组大鼠BALF中总蛋白、总细胞计数及中性粒细胞计数水平分别与空气对照组、UC-MSCs对照组比较,差异均有统计学意义(P<0.05)。UC-MSCs治疗组大鼠BALF中细胞总数、中性粒细胞计数及总蛋白水平均明显低于BPD模型组,差异有统计学意义(P<0.05)。UC-MSCs治疗组大鼠肺泡平均截距低于BPD模型组,而辐射状肺泡计数高于BPD模型组,差异有统计学意义(P<0.05)。UC-MSCs治疗组大鼠外周血IL-1β、IL-8、TNF-α、MDA水平及SOD、MPO活性与BPD模型组比较,差异均有统计学意义(P<0.05)。UC-MSCs治疗组大鼠肺组织中FBN1、FBN2、Fibulin mRNA表达水平较BPD模型组明显下调,且与其他各组比较,差异均有统计学意义(P<0.05)。结论UC-MSCs可通过抑制高氧暴露所致机体氧化应激反应和肺部炎症因子释放,以及阻断肺组织弹性蛋白平衡絮乱,从而减轻新生大鼠高氧肺损伤。

Objective To explore the protective effect of umbilical cord-derived mesenchymal stem cells(UC-MSCs)on hyperoxia induced lung injury in neonatal rats and its molecular mechanism.Methods A total of 96 Sprague Dawley rats were randomly divided into air control group,UC-MSCs control group,BPD model group and UC-MSCs treatment group,24 rats in each group.The changes of body weight,total protein,total cell count,neutrophil count,interleukin(IL)-1β,IL-8,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA)and myeloperoxidase(MPO)in bronchoalveolar lavage fluid(BALF)were compared.And the expression levels of Fibrillin-1(FBN1),FBN2 and Fibulin mRNA in lung tissue of each group were compared.Results There were significant differences in body weight between the UC-MSCs treatment group and the BPD model group on the 14th and 21st day(P<0.05).The total protein,total cell count and neutrophil count in BALF of the BPD model group and the UC-MSCs treatment group were compared with the air control group and the UC-MSCs control group respectively,and the differences were statistically significants(P<0.05).The total number of cells,neutrophil count and total protein level in BALF of the UC-MSCs treatment group were significantly lower than those in the BPD model group(P<0.05).The level of MLI in the UC-MSCs group was lower than that in the BPD group,while the level of RAC in the UC-MSCs group was higher than that in the BPD group(P<0.05).The levels of IL-1β,IL-8,TNF-α,MDA and the activities of SOD and MPO in the peripheral blood of the UC-MSCs group were significantly different from those of the BPD group(P<0.05).The expression levels of FBN1,FBN2 and Fibulin mRNA in lung tissue of the UC-MSCs treated group were significantly lower than those of the BPD model group,and the differences were statistically significant compared with other groups(P<0.05).Conclusion UC-MSCs can reduce the hyperoxia induced lung injury in neonatal rats by inhibiting the oxidative stress response and the release of inflammatory factors in the lung caused by hyperoxia exposure,and by blocking the balance of elastin in the lung.