硝普钠对内毒素致大鼠急性肺损伤保护作用的机制  

Mechanism of protective effect of sodium nitroprusside against endotoxin- induced acute lung injury in rats

作　　者：夏中元[1] 王晓园[1] 杜大平[1] 刘先义[1] 

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《中华麻醉学杂志》2006年第2期148-151,共4页Chinese Journal of Anesthesiology

摘　　要：目的研究外源性一氧化氮(NO)供体-硝普钠对内毒素(LPS)致大鼠急性肺损伤 (ALI)保护作用的机制。方法 32只Wistar大鼠随机分为4组(n=8),假手术组(S组)、内毒素组 (LPS组)、HO-1诱导剂氯化高铁血红素预处理组(HM组)和硝普钠治疗组(SNP组)。采用气管内滴入 750 μg/kg(溶于300 ml生理盐水中)LPS建立大鼠ALI模型,HM组在给LPS前12 h腹腔注射氯化高铁血红素加μmol/kg,SNP组将LPS与硝普钠(25μg/kg)同时滴入气管。滴入LPS后8 h处死大鼠,测定肺组织湿/干重比(W/D)、丙二醛(MDA)含量、诱导型血红素加氧酶(HO-1)、诱导型一氧化氮合酶(iNOS) 蛋白表达及支气管肺泡灌洗液(BALF)蛋白浓度,并观察肺组织病理变化。结果与S组比较,LPS 组、HM组、SNP组肺组织iNOS、HO-1蛋白表达均增强,LPS组、HM组肺组织W/D及MDA含量增加, LPS组BALF蛋白浓度增加;与LPS组比较,HM组和SNP组肺组织iNOS蛋白表达减弱,肺组织HO-1 蛋白表达增强,肺组织W/D、MDA含量及BALF蛋白浓度降低(P<0．05或0．01)。SNP及HM组肺组织病理损伤程度明显轻于LPS组。结论硝普钠可通过诱导HO-1进而抑制iNOS/NO,减轻LPS所致 ALI。Objective To investigate the effect of sodium nitroprusside （SNP）, an exogenous NO donor, on expression of hemeoxygenase-1 （HO-1） and inducible NO synthase （iNOS） in the lung tissue in a rat model of lpopolysaccharide （LPS）-induced acute lung injury and the underlying mechanism. Methods Thirty-two Wistar rats of either sex weighing 190-210 g were randomly divided into 4 groups （ n = 8 each） ： Ⅰ sham operation （S） ; Ⅱ LPS;Ⅲ heroin ＋ LPS and Ⅳ SNP＋ LPS. The animals were anesthetized with intraperitoneal （IP） 7% chloralhydrate 5 ml· kg^-1. LPS 750μg·kg^-1 in 300μl was instilled into the lungs via trachea in group Ⅱ. In group m heroin （a HO- 1 inducer） 40 μmol·kg^-1 was injected IP 12 h before LPS. In group IV SNP 25μg·kg^-1 ＋ LPS 750μg·kg^-1 in 300μl was instilled into the lungs via trachea. In group S normal saline 300/A was instilled via trachea instead of LPS. The animals were killed by （1） exsanguination from carotid artery 8h （2） after LPS instillation and lungs were removed for broncho-alveolar lavage （BAL） and determination of protein concentration in BALF and the expression of HO-1 and iNOS protein in the lung tissue by immuno-histochemical technique and HPIAS-2000 image analysis system and MDA content in lung tissue and （3） light microscopic examination （4） wet/ dry lung weight ratio.Results The 4 groups were comparable with respect to body weight and sex （M/F ratio）. The expression of iNOS and HO-1 in lung tissue was significantly higher in LPS group than in S group （ P 〈 0.01 ） but the increase in iNOS expression was attenuated while the increase in HO-1 expression accentuated by HM pretreatment （group Ⅲ） and SNP administration （group Ⅳ ）. The W/D ratio, protein concentration in BALF and MDA content in lung tissue were all significantly increased by LPS in group Ⅱ as compared to S group and the increases were all attenuated by HM pretreatment （group Ⅲ ） and SNP intratracheal instillation （group

关 键 词：硝普钠 呼吸窘迫综合征 成人 内毒素血症 

分 类 号：R96[医药卫生—药理学]