硫化氢对小鼠血浆P物质的影响及其与肺损伤的相关性  

Effect of Hydrogen Sulfide on Circulatory Level of Substance P and Lung Injury in Mice

作　　者：张绘莉[1] 吴士尧[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院心内科,上海200011

出　　处：《中国临床医学》2010年第3期315-318,共4页Chinese Journal of Clinical Medicine

基　　金：上海高校选拔培养优秀青年教师科研专项基金(编号:jdy08070)

摘　　要：目的:观察硫化氢对小鼠血浆P物质水平的影响及其与肺组织炎性反应和肺微血管通透性的相关性。方法:8周龄、雄性Balb/c小鼠,随机分为对照组(腹腔注射0.9%氯化钠液,注射后1h处死小鼠)、不同剂量硫氢化钠(NaHS)干预组(分别腹腔注射NaHS1mg.kg-1、5mg.kg-1或10mg.kg-1,注射后1h处死小鼠)和NaHS不同时间干预组(腹腔注射NaHS10mg.kg-1,分别于注射后1h、3h或6h处死小鼠),观察血浆P物质水平、肺组织匀浆髓过氧化物酶(MPO)活性和肺微血管通透性。另选,8周龄、雄性、前速激肽原基因敲除小鼠(PPT-A-/-)和相同遗传背景的同龄、野生型Balb/c小鼠(PPT-A+/+),分别随机腹腔注射0.9%氯化钠液或NaHS(10mg.kg-1),注射后1h处死小鼠,观察肺组织MPO活性和肺微血管通透性。结果:硫化氢供体药物—NaHS可显著升高小鼠血浆P物质水平、肺组织匀浆MPO活性和肺微血管通透性,且具有时间和剂量依赖性关系。敲除小鼠编码P物质的PPT-A基因后,10mg.kg-1的NaHS干预则不能显著升高肺组织MPO活性和增加肺微血管通透性。结论:硫化氢可通过促进肺组织炎性反应和增加肺微血管通透性引起肺损伤,其机制可能与升高血浆P物质水平有关。Objective：To investigate the effect of hydrogen sulfide on plasma level of substance P and its relevance to lung inflammation and pulmonary microvascular permeability.Methods： Eight-week old,male Balb/c mice were randomly divided into the following groups： control（saline,i.p.,animals were sacrificed 1h after injection）,sodium hydrosulfide（NaHS） at three doses（1,5,or 10 mg·kg-1,i.p.,animals were sacrificed 1h after injection） and NaHS at three time-point（10 mg·kg-1,i.p.,animals were sacrificed 1h,3h,or 6h after injection）.Thereafter,plasma substance P level,lung myeloperoxidase（MPO） activity and lung microvascular permeability were measured.On the other hand,preprotachykinin-A（PPT-A） gene knockout mice（PPT-A-/-） and their wild-type mice（PPT-A＋/＋） were randomly given saline（i.p.） or NaHS（10 mg·kg-1,i.p.）.One hour after intervention,mice were sacrificed and lung MPO activity and lung microvascular permeability were examined.Results： Hydrogen sulfide donor drug,NaHS significantly elevated plasma substance P level,lung MPO activity and lung microvascular permeability in a time and dose dependent manner.Deletion of PPT-A gene,the precursor gene for substance P,abolished the elevation in lung MPO activity and lung microvascaular permeability induced by injection of NaHS at a dose of 10 mg·kg-1.Conclusions： Hydrogen sulfide may aggravate lung inflammation and impair lung microvascular permeability via increasing plasma level of substance P.

关 键 词：硫化氢 P物质 肺微血管通透性 髓过氧化物酶 

分 类 号：R566[医药卫生—呼吸系统]