HO-1/CO在大鼠内毒素性急性肺损伤中的保护作用及硝普钠对其的影响  

Role of HO-1/CO in Lipopolysaccharide-induced Acute Lung Injury and the Effect of Sodium Nitroprusside on It

作　　者：王晓园[1] 夏中元[1] 杜大平[1] 孟庆涛[1] 

机构地区：[1]武汉大学人民医院麻醉科,武汉430060

出　　处：《武汉大学学报（医学版）》2005年第1期62-65,共4页Medical Journal of Wuhan University

摘　　要：目的 :研究HO 1/CO系统在内毒素 (LPS)致急性肺损伤 (ALI)中的作用 ,并探讨外源性NO供体硝普钠的保护作用机制。方法 :采用LPS气管内滴入建立大鼠ALI模型 ,32只Wistar大鼠随机分为假手术组 (S组 )、内毒素组 (LPS组 )、HO 1诱导剂hemin预处理组 (HM组 )、硝普钠治疗组 (SNP组 )。 8h后取材 ,半定量分析肺组织HO 1表达 ,检测肺湿 /干重比、支气管灌洗液 (BALF)蛋白含量、肺组织MDA含量 ,并观察肺组织病理变化。结果 :与S组比较 ,LPS组HO 1蛋白表达显著增强 (P <0 .0 1) ;hemin预处理和硝普钠治疗后HO 1蛋白表达较LPS组增高 (P <0 .0 1,P <0 .0 5 )。LPS组肺湿 /干重比、BALF中蛋白含量以及组织匀浆MDA含量显著高于S组 (均P <0 .0 1) ,而HM组和SNP组均显著低于LPS组 (P <0 .0 5或P <0 .0 1)。病理形态学 :SNP及HM组病理损伤程度明显轻于LPS组。结论 :HO 1/CO系统参与了LPS致ALI时的肺保护 ;气管内滴注SNP对急性肺损伤的保护作用可能与增强HO 1/CO效应有关。Objective: To investigate the potential role of HO-1/CO systems in LPS-induced acute lung injury (ALI) in rats and to explore the mechanisms of the protective effect of NO donor sodium nitroprusside (SNP) on ALI. Methods: Models of acute lung injury in rats were established through intratracheal instillation of lipopolysaccharide (LPS). Thirty-two Wistar rats were divided randomly into four groups: the sham control group (S group), the LPS intratracheal instillation group (LPS group), the inducer of HO-1 (hemin) pretreatment group (HM group), and the SNP intratracheal administration group (SNP group). The right lung lobes were harvested 8 h after LPS instillation and the left lung lobe was used for bronchoalveolar lavage. The protein expression of HO-1 was observed by using immunohistochemical technique and assessed through HIPAS-2000 image analysis system semi-quantitatively. The lung wet weight to dry weight ratio (W/D), BALF protein, malondialdehyde (MDA) content and lung histopathological changes were detected respectively. Results: Compared with that in S group, the expression of HO-1 was significantly increased in LPS group (P<0.01), but in HM and SNP group, it was much higher than that in LPS group(P<0.01 and P<0.05, respectively). In LPS group, the W/D, BALF protein, and MDA content were obviously higher than those in S group (P<0.01), but they were decreased obviously when pretreated with hemin or administrated of SNP (P<0.05 and P<0.01, respectively). Under microscope, the histopathologic results revealed that the injury in HM and SNP groups was mild as compared with that in LPS proup. Conclusion: The data suggest that the protective effect of HO-1/CO system may be involved in the pathophysiologic procedure of LPS-induced lung injury, and the effect that NO donor-SNP can ameliorate LPS-induced ALI may be related to the up-regulation of HO-1.

关 键 词：诱导型血红素加氧酶 急性肺损伤 内毒素类 硝普钠 

分 类 号：R563[医药卫生—呼吸系统] R363.21[医药卫生—内科学]