LRP1-pPyk2-MMP9通路在高氧诱导新生大鼠肺损伤中的作用  

Role of the LRP1-pPyk2-MMP9 pathway in hyperoxia-induced lung injury in neonatal rats

作　　者：郑亚斐 朱海艳 王维 胡晶晶 包天平[1] 田兆方[1] ZHENG Ya-Fei;ZHU Hai-Yan;WANG Wei;HU Jing-Jing;BAO Tian-Ping;TIAN Zhao-Fang(Department of Neonatology,First Huai'an Hospital Affiliated to Nanjing Medical University/Pediatric Diagnosis and Treatment Respiratory Key Laboratory of Huai'an,Huai'an,Jiangsu 223300,China)

机构地区：[1]南京医科大学附属淮安第一医院新生儿科/淮安市小儿呼吸诊疗重点实验室,江苏淮安223300

出　　处：《中国当代儿科杂志》2021年第12期1289-1294,共6页Chinese Journal of Contemporary Pediatrics

摘　　要：目的探讨低密度脂蛋白受体相关蛋白1(low-density lipoproteinreceptor-related protein 1,LRP1)-磷酸化酪氨酸激酶2(proline-rich tyrosinekinase 2 phosphorylation,pPyk2)-基质金属蛋白酶9(matrix metalloproteinases 9,MMP9)通路在高氧诱导新生大鼠肺损伤中的作用。方法将16只新生大鼠随机分为空气组和高氧组,每组8只。高氧组大鼠于生后即置于吸入氧浓度>95%的环境中7 d,空气组大鼠置于同室空气环境中;第8天处死全部大鼠。苏木精-伊红染色法观察两组大鼠肺组织病理变化;ELISA法检测血清及支气管肺泡灌洗液中可溶性LRP1(sLRP1)、MMP9水平;Western blot法检测肺组织LRP1、MMP9、pPyk2及Pyk2蛋白表达水平;RT-PCR法检测肺组织LRP1 mRNA及MMP9 mRNA表达水平。结果血清和支气管肺泡灌洗液中sLRP1、MMP9在高氧组的水平均高于空气组(P<0.05);高氧组肺组织匀浆LRP1、MMP9、pPyk2蛋白表达水平较空气组显著升高(P<0.05);肺组织LRP1 mRNA、MMP9 mRNA在高氧组的相对表达量显著高于空气组(P<0.05)。结论LRP1-pPyk2-MMP9通路在高氧诱导新生大鼠肺损伤中活化增强,可能参与支气管肺发育不良的发病机制。Objective To study the role of the low-density lipoprotein receptor-related protein 1(LRP1)-proline-rich tyrosine kinase 2 phosphorylation(pPyk2)-matrix metalloproteinases 9(MMP9)pathway in hyperoxia-induced lung injury in neonatal rats.Methods A total of 16 neonatal rats were randomly placed in chambers containing room air(air group)or 95%medical oxygen(hyperoxia group)immediately after birth,with 8 rats in each group.All of the rats were sacrificed on day 8 of life.Hematoxylin and eosin staining was used to observe the pathological changes of lung tissue.ELISA was used to measure the levels of soluble LRP1(sLRP1)and MMP9 in serum and bronchoalveolar lavage fluid(BALF).Western blot was used to measure the protein expression levels of LRP1,MMP9,Pyk2,and pPyk2 in lung tissue.RT-PCR was used to measure the mRNA expression levels of LRP1 and MMP9 in lung tissue.Results The hyperoxia group had significantly higher levels of sLRP1 and MMP9 in serum and BALF than the air group(P<0.05).Compared with the air group,the hyperoxia group had significant increases in the protein expression levels of LRP1,MMP9,and pPyk2 in lung tissue(P<0.05).The hyperoxia group had significantly higher relative mRNA expression levels of LRP1 and MMP9 in lung tissue than the air group(P<0.05).Conclusions The activation of the LRP1-pPyk2-MMP9 pathway is enhanced in hyperoxia-induced lung injury in neonatal rats,which may be involved in the pathogenesis of bronchopulmonary dysplasia.

关 键 词：肺损伤 高氧 低密度脂蛋白受体相关蛋白1 基质金属蛋白酶 大鼠 

分 类 号：R722.6[医药卫生—儿科]