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临床相关剂量参附注射液预处理和后处理对大鼠肠缺血再灌注致急性肺损伤的影响

The protective effects of preconditioning and postconditioning clinical use of SFI on lung injury induced by intestinal ischemia-reperfusion in rats
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摘要 目的探讨临床相关等效剂量参附注射液(shenfu injection,SFI)预处理和后处理对大鼠肠缺血再灌注致急性肺损伤的影响。方法建立肠缺血再灌注致急性肺损伤模型。健康大鼠随机分成7组,每组8只:对照组(C组):肠系膜上动脉仅分离而不阻断;损伤组(I/R组):肠系膜上动脉阻断1 h后再灌注2 h,股静脉给予等量生理盐水进行对照;参附注射液预处理组(SFPR组):肠系膜上动脉阻断前1 h将10 m L·kg-1的参附注射液从股静脉恒速泵入;参附注射液后处理组(SFPO组):肠系膜上动脉阻断1 h后将10 m L·kg-1的参附注射液从股静脉恒速泵入;血晶素组(Hemin组):肠系膜上动脉阻断前24 h腹腔注射Hemin 75μmol·kg-1。锌原卟啉IX+SFPR组(Zn PPIX+SFPR组):肠系膜上动脉阻断前24 h腹腔注射锌原卟啉IX(20mg·kg-1),后续操作同SFPR组;锌原卟啉IX+SFPO组(Zn PPIX+SFPO组):肠系膜上动脉阻断前24 h腹腔注射锌原卟啉IX(20 mg·kg-1),后续操作同SFPO组。术前无需给药的各组腹腔注射等剂量的生理盐水,于再灌注2 h后颈动脉放血处死动物。观察肺组织中血红素加氧酶1(HO-1)的表达,丙二醛(MDA)、过氧化物歧化酶(SOD)含量和肺通透性指数、动脉血气和湿重比值的影响。结果与I/R组比较,SFPR组、SFPO组和Heim组肺组织HO-1细胞阳性表达增高;Zn PPIX+SFPR组和Zn PPIX+SFPO组上述阳性细胞表达降低(P<0.05)。SFPR组、SFPO组和Heim组肺通透性指数、肺组织MDA含量和湿/干重比均显著降低,SOD值明显升高(P<0.05或P<0.01);与C组比较,I/R组肺通透性指数与肺组织MDA含量和湿/干重比明显增高,而SOD含量显著降低(P<0.05);各组动物动脉血Pa O2、Pa CO2较C组显著下降(P<0.05),SFPR组、SFPO组和Heim组Pa O2、Pa CO2明显高于I/R组。结论临床相关剂量的参附注射液预处理和后处理均能明显减轻肠缺血再灌注导致的急性肺损伤,其机制与上调HO-1蛋白表达、一定程度上抑制脂质过氧化、拮抗氧自 Objective To investigate the protection and mechanism of clinical use of SFI on lung injury induced by intestinal ischemia- reperfusion in rats. Methods Established the acute lung injury models caused by gastrointestinal mucosa of ischemia reperfusion. Healthy rats were divided into 7 groups,with 8 rats in each group:( 1) Control group( group C) : Just separated the SMA but not block;( 2) Injury group( I / R group) : Established the ischemia reperfusion models by blocking SMA for 1 h and then reperfused for 2 h,and intravenously injected equivalent NS;( 3) Preconditioning rats with SFI( group SFPR) : Intravenously injected SFI 10 m L·kg^-11 h before blocking SMA;( 4) Postconditioning rats with SFI( group SFPO) : Intravenously injected SFI 10 m L·kg^-11 h after blocking SMA;( 5) Hemin group: Intraperitoneally injected Hemin 75 μmol·kg^-124 h before blocking SMA. Rats were then sacrificed 2 h after reperfusion.( 6) Zn PPIX + SFPR group: Intraperitoneally injected Zn PPIX 20 mg·kg^-1·day- 124 h before blocking SMA,and the remaining steps were the same as SFPR group.( 7) Zn PPIX + SFPO group:Intraperitoneally injected Zn PPIX 20 mg·kg^-1·day- 124 h after blocking SMA,and the remaining steps were the same as SFPO group. HO-1levels in lung tissues,malondialdehyde( MDA) and superoxide dismutase( SOD),permeability index of lung,artery blood gas and W/ D ratio were observed and recorded in the meantime. Results( 1) Compared with group I / R,HO-1 levels in lung tissues of groups SFPR,SFPO and Hemin were higher,while lower in groups of Zn PPIX + SFPR and Zn PPIX + SFPO.( 2) Permeability index of lung and MDA concentration in group I / R were significantly higher than group C,but lower regarding SOD( P〈0. 05),which was not the case in groups SFPR,SFPO and Heim.( 3) Compared with group C,the W/ D ratio in group I / R has increased significantly( P〈0. 01),but decreased in groups SFPR,SFPO and Heim( P〈0. 05). Pa O2
出处 《安徽医药》 CAS 2015年第11期2057-2060,共4页 Anhui Medical and Pharmaceutical Journal
基金 湖北省公益性科技研究计划(No 2013BKB014)
关键词 再灌注损伤 肺脏 肠黏膜 血红素加氧酶-1 参附注射液 reperfusion injury lung intestinal mucosa heme oxygenase-1 Shenfu injection
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