地塞米松对哮喘小鼠感觉神经肽P物质表达的影响  

Effect of dexamethasone on expression of sensory neuropeptide substance P in asthmatic mice

作　　者：王植嘉[1] 尚云晓[1] Wang Zhijia;Shang Yunxiao(Department of Respiratory Pediatrics,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院小儿呼吸内科,沈阳110004

出　　处：《国际儿科学杂志》2020年第8期573-577,共5页International Journal of Pediatrics

基　　金：辽宁省教育厅辽宁省高等学校创新团队支持计划(辽教函(2018)479号)。

摘　　要：目的探讨地塞米松对哮喘小鼠感觉神经肽P物质(substance P,SP)表达的影响。方法6~7周龄BALB/c小鼠32只,随机分为4组:对照组、哮喘组、WIN 62,577(SP受体拮抗剂)干预组、地塞米松干预组。卵蛋白(ovalbumin,OVA)致敏及激发建立小鼠急性哮喘模型;WIN 62,577干预组在每次激发前1 h腹腔注射WIN 62,577300μg,每天1次,连续7 d;地塞米松干预组在每次激发前1h腹腔注射地塞米松2 mg/kg,每天1次,连续7 d。酶联免疫吸附(enzyme linked immunosorbent assay,ELISA)测定各组小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)及血清中SP水平变化。免疫组化观察SP及其受体神经激肽1受体(neurokinin 1 receptor,NK-1R)在小鼠肺组织表达定位情况。结果ELISA结果显示哮喘组小鼠BALF中SP水平[(45.78±9.15)ng/L]明显高于对照组[(17.02±2.80)ng/L](P<0.01);WIN 62,577干预组[(25.26±3.48)ng/L]与哮喘组[(45.78±9.15)ng/L]比较,BALF中SP水平显著降低(P<0.01);与哮喘组[(45.78±9.15)ng/L]比较,给予地塞米松干预后BALF中SP水平[(34.03±4.38)ng/L]显著降低(P=0.002)。与对照组[(6883.32±1734.89)ng/L]比较,哮喘组小鼠血清中SP水平[(10247.62±2667.38)ng/L]明显增高(P=0.001);与哮喘组[(10247.62±2667.38)ng/L]比较,WIN 62,577干预组血清中SP水平[(4285.99±1926.36)ng/L]显著降低(P<0.01);与哮喘组[(10247.62±2667.38)ng/L]比较,给予地塞米松干预后血清中SP水平[(6787.22±1907.45)ng/L]显著降低(P=0.001)。免疫组化结果显示在小鼠气道上皮、血管周围、平滑肌层均可见SP及NK-1R表达;与对照组比较,SP及NK-1R在哮喘组小鼠气道内表达明显增加;与哮喘组比较WIN 62,577干预组与地塞米松干预组气道SP及NK-1R表达明显降低。结论地塞米松抑制哮喘小鼠气道感觉神经肽SP的表达。Objective To explore the effect of dexamethasone on the expression of sensory neuropeptide substance P(SP)in asthmatic mice.Methods Thirty-two BALB/c mice 6~7 weeks were randomly divided into 4 groups:control group,asthmatic group,WIN 62,577(SP receptor antagonist)intervention group and dexamethasone intervention group.The acute asthma models were established in BALB/c mice by sensitizing and challenging with ovalbumin.The WIN 62,577 intervention group was given WIN 62,577300μg intraperitoneal injection 1h before each challenge,once a day for 7 consecutive days;the dexamethasone group was given intraperitoneal injection of dexamethasone 2 mg/kg 1h before each challenge,once a day for 7 consecutive days.Results ELISA results showed that the level of SP[(45.78±9.15)ng/L]in BALF in the asthmatic group was significantly higher than that in the control group[(17.02±2.80)ng/L](P<0.01);the SP level in BALF in the WIN 62,577 intervention group[(25.26±3.48)ng/L]was significantly lower than that in the asthmatic group[(45.78±9.15)ng/L](P<0.01);compared with the asthmatic group[(45.78±9.15)ng/L],the SP level in BALF was significantly reduced after dexamethasone intervention[(34.03±4.38)ng/L](P=0.002).Compared with the control group[(6883.32±1734.89)ng/L],the level of SP in the serum of mice in the asthmatic group[(10247.62±2667.38)ng/L]was significantly higher(P=0.001);compared with the asthmatic group[(10247.62±2667.38)ng/L],the level of SP in the serum of the WIN 62,577 intervention group[(4285.99±1926.36)ng/L]was significantly lower(P<0.01);compared with the asthmatic group[(10247.62±2667.38)ng/L],the serum SP level was significantly reduced after dexamethasone intervention[(6787.22±1907.45)ng/L](P=0.001).The results of immunohistochemistry showed that SP and NK-1R expression could be seen in the mouse airway epithelium,perivascular and smooth muscle layer;compared with the control group,SP and NK-1R expression in the airway of asthmatic mice was significantly increased;compared with the asthmatic group,SP a

关 键 词：哮喘 感觉神经肽 P物质 地塞米松 小鼠 

分 类 号：R965[医药卫生—药理学]