香叶木素对胎粪诱导的新生大鼠急性肺损伤的作用及其机制探讨  

Effect of Diosmetin on Acute Lung Injury Induced by Meconium and Its Mechanism in Neonatal Rats

作　　者：郝莉霞[1] 卢蓉[2] 马霞霞[1] 樊书娟[3] HAO Lixia;LU Rong;MA Xiaxia;FAN Shujuan(Department of Neonatology,Affi lia/ed Hospital of Yan'an University,Yan'an 716000,China;Department of Pediatrics 1 Ward,Affiliated Hospital of Yan'an University,Yan'an 716000,China;Department of Pediatrics,First Afftliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]延安大学附属医院新生儿科,延安716000 [2]延安大学附属医院儿科一病区,延安716000 [3]西安交通大学第一附属医院新生儿科,西安710061

出　　处：《实验动物与比较医学》2020年第5期384-390,共7页Laboratory Animal and Comparative Medicine

基　　金：陕西省社会发展科技攻关项目(2015SF037)。

摘　　要：目的探讨香叶木素对胎粪诱导的新生大鼠急性肺损伤的作用及其分子机制。方法48只1日龄SPF级雄性SD大鼠由气管插管注入胎粪1.5 mL/kg,建立胎粪肺损伤模型。大鼠随机分为4组:对照组、模型组、甲强龙组和香叶木素组。全自动血气分析仪检测各组大鼠的动脉氧合指数。HE染色检测大鼠肺组织病理损伤程度,并进行肺损伤病理评分。肺损伤模型建立24 h后,切除肺组织,称取其质量;酶联免疫吸附测定法检测炎性因子如肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)和IL-6水平;蛋白质印迹法检测含pyrin结构域的NOD样受体蛋白3(NOD-like receptor with pyrin domain 3,NLRP3)炎性小体、剪切型半胱天冬酶1(cleaved caspase-1,c-caspase-1)和IL-1β蛋白水平。结果与模型组相比,甲强龙组与香叶木素组大鼠的平均动脉氧合指数明显降低(均P<0.05),病理损伤程度及肺损伤病理评分明显降低(均P<0.05),炎性因子TNF-α、IL-1β和IL-6水平明显降低(均P<0.01),NLRP3、c-caspase-1和IL-1β蛋白表达明显下调(均P<0.01)。结论香叶木素通过降低动脉氧合指数及炎性因子表达水平,并下调NLRP3、c-caspase-1和IL-1β蛋白表达水平,对胎粪诱导的新生大鼠急性肺损伤具有一定的治疗作用。Objective To investigate the therapeutic effect of diosmetin on fetal faecal-induced acute lung injury in neonatal rats.Methods Fourty-eight neonatal male SD rats were enrolled.The rats were injected with 1.5 mL/kg fetal faecal by endotracheal intubation to replicate meconium lung injury model and randomly divided into 4 groups:control group,model group,methylprednil group and diosmetin group for subsequent experiments.Automatic blood gas analyzer was used to detect the arterial oxygenation index.Hematoxylin-eosin(HE)dye was used to detect the degree of lung tissue pathological injury and to evaluate the pathological score of lung injury.The lung tissue was removed and weighed 24 h after the establishment of lung injury model.The levels of inflammatory cytokines including tumor necrosis factor-alpha(TNF-α),interleukin-1 beta(IL-1β)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.The expressions of NOD-like receptor with pyrin domain 3(NLRP3)inflammasome,cleaved caspase-1(c-caspase-1)and IL-1β proteins were detected by Western blotting.Results Compared with the model group,the mean arterial oxygenation index of methylprednil group and diosmetin group decreased significantly(both P<0.05),and the pathological damage degree and lung injury pathological score were significantly reduced(both P<0.05),the levels of inflammatory factors TNF-α,IL-6 and IL-1β as well as the expressions of NLRP3,c-caspase-1 and IL-1β proteins were significantly lower(all P<0.01).Conclusion Diosmetin can down-regulate the levels of NLRP3,c-caspase-1 and IL-1β,as well as reduce the arterial oxygenation index and the levels of inflammatory cytokines,thereby can be used to treat neonatal rats with meconium-induced acute lung injury.

关 键 词：香叶木素 胎粪吸入性肺炎 炎性因子 NOD样受体蛋白3 SD大鼠 

分 类 号：Q95-33[生物学—动物学]