塞来昔布对新生大鼠高氧致肺损伤的干预作用  

Intervention of celecoxib on lung injury induced by hyperoxia in neonatal rats

作　　者：周福根[1] 魏婷[1] 游晏平 李建国[1] 龙文香[1] ZHOU Fu-gen;WEI Ting;YOU Yan-ping;LI Jian-guo;LONG Wen-xiang(Department of Neonatology,Ji’an Maternal and Child Health Hospital,Ji’an 343000,Jiangxi Province,China)

机构地区：[1]吉安市妇幼保健院新生儿科,江西吉安343000

出　　处：《中国临床药理学杂志》2023年第8期1113-1116,共4页The Chinese Journal of Clinical Pharmacology

基　　金：江西省卫生健康委员会科技计划基金资助项目(202140975)。

摘　　要：目的探讨塞来昔布对高氧致新生大鼠肺损伤的影响,并分析可能的作用机制。方法以持续暴露在高浓度氧中的方法建立新生大鼠肺损伤模型。将30只新生大鼠随机分为对照组(n=10)、模型组(n=10)、实验组(n=10)。实验组于模型建立成功后腹腔注射1.5 mg·kg^(-1)塞来昔布(连续7 d)。对照组、模型组于相同时间点腹腔注射等量0.9%NaCl。以苏木精-伊红(HE)染色法观察大鼠肺组织病理学变化;以酶联免疫吸附法(ELISA)测定各组肺组织中活性氧簇(ROS)水平;以蛋白质印迹法测定各组大鼠肺组织中核因子-κB/诱导型一氧化氮合酶(NF-κB/iNOS)信号通路相关蛋白表达水平。结果对照组肺组织肺泡结构完整,肺泡壁未增厚,未见充血及炎性细胞浸润;模型组肺泡间隙增加且充血水肿,肺泡腔可见炎性渗出液,肺组织结构紊乱;与模型组比较,实验组病理变化明显减轻。对照组、模型组和实验组大鼠的肺组织ROS浓度分别为(285.79±35.55)、(456.77±63.23)和(389.87±53.77)U·mL^(-1);NF-κB p65蛋白表达水平分别为0.19±0.03、1.06±0.16和0.89±0.13;iNOS蛋白表达水平分别为0.33±0.06、1.23±0.18和0.96±0.13。模型组、实验组上述指标与对照组比较,差异均有统计学意义(P<0.01或P<0.05);实验组的上述指标与模型组比较,差异均有统计学意义(P<0.01或P<0.05)。结论塞来昔布对高氧致新生大鼠肺损伤具有保护作用,可能是通过抑制氧化应激,进而抑制NF-κB/iNOS信号通路活化实现的。Objective To investigate the effect of celecoxib on hyperoxia-induced lung injury in neonatal rats and to analyze the possible mechanism.Methods The neonatal rat model of lung injury was established by continuous exposure to high concentration oxygen.Thirty newborn rats were randomly divided into control group(n=10),model group(n=10)and experimental group(n=10).Model group and experimental group were exposed to hyperoxic to establish hyperoxic lung injury model,and experimental group was injected intraperitoneally with 1.5 mg·kg^(-1) celecoxib(once a day for 7 days).The control group and the model group were injected with the same amount of normal saline at the same time point.The pathological changes of lung tissue were observed by Hematoxylin and eosin(HE);the levels of reactive oxygen species(ROS)in lung tissue were measured by Elisa;the expression of nuclear factor kappa-B/inducible nitric oxide synthase(NF-κB/iNOS)signal pathway was detected by Western blotting.Results In the con tro l group,the alveolar structure was intact,the alveolar wall was not thickened,and no congestion or inflammatory cell infiltration was observed.In the model group,the alveolar space was increased,congestion and edema were observed,inflammatory exudate was observed in the alveolar cavity,and the structure of lung tissue was disordered.Compared with the model group,the pathological changes in the experimental group were significantly reduced.In control group,model group and experimental group,the ROS concentration were(285.79±35.55),(456.77±63.23),(389.87±53.77)U·mL^(-1),respectively;the expression levels of NF-κB p65 protein were 0.19±0.03,1.06±0.16 and 0.89±0.13,respectively;the expression levels of iNOS were 0.33±0.06,1.23±0.18 and 0.96±0.13,respectively.The expressions of ROS,NF-κB p65 and iNOS in lung tissue of rats in model group and experimental group were significantly higher than those in the control group(P<0.01 or P<0.05);the above indexes in experimental group were significantly lower than those in model g

关 键 词：塞来昔布 肺损伤 新生大鼠 核因子-ΚB 诱导型-氧化氮合酶 

分 类 号：R974[医药卫生—药品]