HO-1/CO径路在肺缺血-再灌注损伤中的作用  

Role of heme oxygenase-1/carbon monoxide system in pulmonary ischemiareperfusion injury

作　　者：王万铁[1] 周伟斌[1] 倪世蓉[1] 徐正祄[1] 陈锡文[2] 方周溪[3] 

机构地区：[1]温州医学院病理生理学教研室,浙江温州325027 [2]温州医学院实验动物中心,浙江温州325027 [3]温州医学院电镜室,浙江温州325027

出　　处：《中国病理生理杂志》2005年第9期1739-1743,共5页Chinese Journal of Pathophysiology

基　　金：浙江省跨世纪学术和技术带头人培养基金(No.992086);温州市"551人才工程"培养基金(No.98113);浙江省教育厅科研基金(No.20000670)资助项目

摘　　要：目的:探讨血红素氧合酶-1(HO-1)/一氧化碳(CO)径路在肺缺血-再灌注损伤中的作用。方法:采用在体兔单肺原位缺血-再灌注模型。实验兔40只,随机均分为假手术对照(C)组、肺缺血-再灌注(I-R)组、肺缺血-再灌注加氯铁血红素(H)组和肺缺血-再灌注加锌原卟啉(Z)组。分别在缺血前、缺血后、再灌注1h、2h、3h抽血,检测一氧化碳血红蛋白(COHb)浓度。实验结束时取肺组织检测湿干重比(W/D)、肺泡损伤率(IAR),观察肺组织超微结构的改变、HO-1的活力、表达部位及强度。结果:血浆COHb浓度,I-R组、H组明显高于C组,以H组为著(P<0.01);H组、Z组显著高于、低于I-R组(P<0.01)。肺组织HO-1活力H组最高,其次是I-R组,Z组和C组最低(P<0.05和P<0.01)。I-R组、H组、Z组HO-1在肺血管内皮、部分血管平滑肌、外膜层及部分气道上皮均有阳性表达,明显高于C组,尤以H组最为明显(P<0.01)。W/D、IAR值,I-R组和Z组均明显高于C组,尤以Z组为著,H组虽较C组为高,但显著低于IR组和Z组(P<0.05和P<0.01)。肺组织形态学异常改变,以Z组为著,H组较轻。结论:HO-1/CO径路对缺血-再灌注肺发挥积极的保护作用。AIM： To investigate the effect of heme oxygenase- 1 （HO- 1 ）/carbon monoxide （CO） system on pulmonary isehemia- reperfusion injury （Hill） in rabbits. METHODS： Single lung ischemia and reperfusion animal model was used in vivo. The rabbits were randomly divided into three groups （ n = 10 in each）, control group （C）, PIR group （ I - R）, PIR ＋ hemin group （H） and PIR＋ zinc protoporphyrin 1X （ZnPP） group （Z）. Changes of several parameters which included plasma carboxyhemoglobin （COHb） at different time points, wet to dry ratio of lung tissue weight （W/D）, the injured alveoli rate （IAR） and the HO- I enzymatic activity were measured at 180 min after reperfusion in lung tissue. The tissue slides were also stained by immunohistrx：hemistry （IHC） and in situ hybridization （ISH） for HO- I to detect the expression of HO- 1 in lung and to analyze the optical density. The lung tissue was prepared for electron microscopic observation at 180 rain after reperfusion. RESULTS： The plasma content of COHb in I - R, H, and Z group increased in a time-dependent manner after I - R. But the increment of H group was higher than that of I - R group, while that of Z group was lower. The HO - 1 activity in lung tissue was highest in H group, followed by IR group, Z group, and C group （P〈0.05 and P〈0.01）. Except C group, HO- 1 was upregulated in all other groups in the pulmonary, endothelial cells, part of puhnonary vascular smooth muscle cells, extima of vessels and epithelial cells of airway. H group had the highest average optical density value, then the IR group, Z group and C group （ P 〈 0.05 and P 〈 0.01 ）. The value of W/D and IAR was highest in Z group, the second was in IR group, then the H group and C group （ P 〈 0.05 and P 〈 0.01 ）. The ＇abnormal changes of the lung tissue in morphology in I - R group, Heroin treatment mitigated the injury of I- R in H group and ZnPP exacerbated the impaiment of ultrastructure in Z group were also observe

关 键 词：再灌注损伤 肺 血红素氧合酶(脱环) 一氧化碳 

分 类 号：R363[医药卫生—病理学]