摘要
目的探讨肝素对支气管肺发育不良(BPD)新生鼠血清及肺组织中性粒细胞诱捕网(NETs)的影响。方法将新生SD大鼠随机分为空气组、高氧组、肝素组、对照组,每组12只。空气组置于空气中,其他3组置于氧浓度为90%的高氧箱7d建立BPD模型。肝素组于造模开始后,每天腹腔注射低剂量肝素(250U/kg)至造模结束;对照组每天腹腔注射等量0.9%氯化钠溶液。分别在出生后第7、14天,每组各取6只麻醉并采集血液标本及肺组织标本,采用PicoGreen荧光染色法检测血清游离DNA(cf-DNA/NETs)水平,共聚焦显微成像观察肺组织NETs,HE染色观察肺组织形态学并测定肺泡辐射状计数(RAC)和平均内衬间隔(MLI)。结果出生后第7、14天,高氧组、对照组新生鼠血清游离DNA水平较空气组明显升高(均P<0.05),肝素组较高氧组明显降低(P<0.05)。在荧光显微镜下观察,高氧组、对照组肺组织组蛋白、髓过氧化物酶荧光信号范围增加,NETs表达增加;肝素组荧光信号范围减少。与空气组比较,高氧组、对照组新生鼠RAC明显减少,MLI明显增加,差异均有统计学意义(均P<0.05);与高氧组比较,肝素组RAC明显增加,MLI明显减少,差异均有统计学意义(均P<0.05)。结论高氧致BPD新生鼠血清及肺组织中存在大量NETs,肝素可抑制NETs产生,并改善高氧引起的肺发育受阻。
Objective To investigate the effect of heparin on neutrophil extracellular traps(NETs)in serum and lung tissue of neonatal rats with hyperoxia-induced bronchopulmonary dysplasia(BPD).Methods Newborn SD rats were randomly divided into air group,hyperoxia group,heparin group and control group,with 12 rats in each group.All animals,except those of air group,were exposed to 90%oxygen continuously for 7d to induce BPD.The rats in heparin group were intraperitoneally injected withlow dose of heparin(250 U/kg)daily until the end of modeling,the control group were injected with same volume of 0.9%sodium chloride solution.Six rats in each group were sacrificed at d7 and d14,respectively,the blood and lung tissue samples were collected.The serum free DNA(cfDNA/NETs)levels were detected using PicoGreen fluorescent staining method,lung tissue NETs were observed by confocal microscopy imaging,the Radical Alveolar Count(RAC)and Mean Linear Intercept(MLI)in lung tissue were measured.Results The serum free DNA levels in the hyperoxia group and control group were significantly higher than that in the air group(all P<0.05),while that in the heparin group was significantly lower(P<0.05).Compared with air group,the fluorescence signal range of histones,myeloperoxidase,and the expression of NETs in lung tissues of hyperoxia group and control group were increased,while those in heparin groupdecreased on d7 and d14.Compared with the air group,neonatal rats RAC in the hyperoxia group and the control group decreased significantly,while MLI increased significantly(all P<0.05).Compared with the hyperoxia group,RAC significantly increased and MLI significantly decreased in the heparin group(all P<0.05).Conclusion Large mount of NETs exist in serum and lung tissues of neonatal rats with high oxygen-inducedBPD,heparin can inhibit the production of NETs and may attenuate hyperoxide-induced pulmonary development arrest.
作者
盛安群
陈翠娥
孙媛媛
张希希
钱燕
朱融和
周爱华
王楸
冯建华
SHENG Anqun;CHEN Cui’e;SUN Yuanyuan(Department of Pediatrics,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;不详)
出处
《浙江医学》
CAS
2019年第23期2482-2485,I0002,共5页
Zhejiang Medical Journal
基金
温州市科技局项目（Y20140497）
义乌市科技局项目（19-3-100）
关键词
肝素
中性粒细胞诱捕网
支气管肺发育不良
高氧
Heparin
Neutrophil extracellular traps
Bronchopulmonary dysplasia
Hyperoxia
