CD163/TWEAK通路对动脉粥样硬化的作用

目的:探讨CD163/肿瘤坏死因子样凋亡弱诱导因子(TWEAK)途径对小鼠动脉粥样硬化的影响。方法:以8～10周的载脂蛋白E基因敲除(APOE~(-/-))及野生型(WT)C57BL/6小鼠为研究对象,分为以下4组(n=10):APOE~(-/-)+普食(ND)组、APOE~(-/-)+高脂饮食(WD)组、WT+ND组和WT+WD组。喂养16周后检测血脂水平,主动脉油红O染色测定主动脉斑块面积以明确成功建立动脉粥样硬化模型;Western blot法检测各组小鼠主动脉CD163和TWEAK的蛋白表达水平;免疫组化法明确动脉粥样硬化斑块CD163与TWEAK的表达及空间分布特征;细胞实验研究CD163对1型巨噬细胞(M1)及泡沫细胞TWEAK的调节作用及其可能的下游作用途径。结果:血脂检测及主动脉油红O染色结果显示,APOE~(-/-)+ND及APOE~(-/-)+WD组小鼠成功建立动脉粥样硬化模型。免疫组化可见CD163主要表达于远离脂质核心的部位,而TWEAK可见于动脉粥样硬化斑块的所有部位。主动脉Western blot检测结果显示,与WT小鼠相比,APOE~(-/-)小鼠主动脉CD163的表达水平显著增加(P0.05),与之相对应的是APOE~(-/-)小鼠主动脉中TWEAK表达水平较WT小鼠亦显著升高(P0.05)。细胞实验结果显示CD163可显著抑制TWEAK的蛋白表达,明显下调核因子κB(NF-κB)的水平(P0.05)。结论:CD163可通过抑制TWEAK/NF-κB途径而发挥抗动脉粥样硬化作用。     

南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CIMO配体表达、巨噬细胞和平滑肌细胞数量的影响

目的：探讨南蛇藤素对高脂饲养ApoE基因敲除小鼠（ApoE^-/-）主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响。方法：8周龄雄性ApoE^-/-小鼠12只,随机分为南蛇藤素组或二甲基亚砜（DMSO）溶剂对照组,每组各6只。均给以高脂饲养8周,在高脂饲养的后4周,分别给予南蛇藤素2mg·kg^-1·d^-1或相当剂量的DMSO腹腔注射（ip）4周。麻醉处死小鼠后,取小鼠主动脉,以石蜡包埋,行主动脉根部连续切片。免疫组化法检测主动脉粥样硬化斑块内CD40配体、CD68和平滑肌α-actin表达水平,以Image ProPlus6．0软件进行图像分析。结果：与对照组相比,南蛇藤素组主动脉粥样硬化斑块内CD40配体表达显著减少（P〈0．05）;巨噬细胞的阳性率显著降低（P〈0．05）;而两组问动脉粥样硬化斑块内平滑肌细胞的阳性率没有显著差异（P〉0．05）。结论：南蛇藤素可能通过减少ApoE^-/-小鼠粥样斑块内CD40配体的表达和巨噬细胞的聚集,抑制动脉粥样硬化斑块中炎症反应,而发挥稳定动脉粥样硬化斑块的作用。     

苯那普利对兔主动脉粥样硬化斑块和血脂的影响

目的 苯那普利是否具有抑制实验性动脉粥样硬化斑块形成的作用。方法 血清TC、TG、LDL－C、HDL-C，定性定量分析主动脉病变面积。结果 高脂组（AS组）和给药组（L组）血脂水平比正常对照组（C组）明显升高（P＜0.01)，L组动脉粥样硬化斑块面积／血管内膜面积、平均最大内膜厚度、平均最大内膜／中膜均明显低于AS组（P＜0.01)。结论 苯那普利能有效抑制动脉粥样硬化的形成和发展。     

辛伐他汀对动脉粥样硬化家兔血管壁NF—κB—DNA结合活性与MCP-1表达的影响

目的观察辛伐他汀对兔动脉粥样硬化斑块中核因子-κB（NF-κB）．DNA结合活性与单核细胞趋化因子-1（MCP-1）表达的影响，探讨辛伐他汀降脂效应以外的抗动脉粥样硬化（AS）作用机制。方法36只雄性新西兰大耳白兔被随机分为低脂对照组（LC）、高脂对照组（HC）和辛伐他汀组（HC＋S）。实验中动态观察血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-C）的变化；实验结束时，用电泳移动迁移技术（EMSA）检测三组兔主动脉组织中NF-κB-DNA结合活性；用免疫组化技术观察各组血管组织中MCP-1的表达；显微镜下测定各组主动脉内膜厚度与粥样斑块面积。结果实验结束时，HC＋S与LC组的TC、TG、LDL-C水平、NF-κB-DNA结合活性、MCP-1表达、主动脉内膜厚度和粥样斑块面积均明显小于HC组（P〈0．05）；HC＋S组的的TC、TG和LDL-C水平与LC组相比虽无明显差异（P〉0．05），但其NF-κB-DNA结合活性、MCP-1表达、内膜厚度和粥样斑块面积均小于LC组（P〈0．05）。结论辛伐他汀可以通过抑制NF-κB-DNA结合活性、减弱MCP-1表达而减轻AS的形成。     

南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响

目的:探讨南蛇藤素对高脂饲养ApoE基因敲除小鼠(ApoE-/-)主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响。方法:8周龄雄性ApoE-/-小鼠12只,随机分为南蛇藤素组或二甲基亚砜(DMSO)溶剂对照组,每组各6只。均给以高脂饲养8周,在高脂饲养的后4周,分别给予南蛇藤素2 mg·kg-1·d-1或相当剂量的DMSO腹腔注射(ip)4周。麻醉处死小鼠后,取小鼠主动脉,以石蜡包埋,行主动脉根部连续切片.。免疫组化法检测主动脉粥样硬化斑块内CD40配体、CD68和平滑肌α-actin表达水平,以Image Pro Plus 6.0软件进行图像分析。结果:与对照组相比,南蛇藤素组主动脉粥样硬化斑块内CD40配体表达显著减少(P＜0.05);巨噬细胞的阳性率显著降低(P＜0.05);而两组间动脉粥样硬化斑块内平滑肌细胞的阳性率没有显著差异(P＞0.05)。结论:南蛇藤素可能通过减少ApoE-/-小鼠粥样斑块内CD40配体的表达和巨噬细胞的聚集,抑制动脉粥样硬化斑块中炎症反应,而发挥稳定动脉粥样硬化斑块的作用。     

内源性HO-1/CO系统在动脉粥样硬化发病中的作用

目的探讨血红素氧合酶-1(HO-1)/一氧化碳(CO)系统在动脉粥样硬化(AS)中的变化、对AS进程的影响及其可能的作用机制。方法家兔予以高胆固醇饮食以及在高胆固醇(n=8)饮食的同时经腹腔注射血红素-L-赖氨酸盐(n=8)或ZnPP-IX(n=8)共10周。结果与正常对照组比较,胆固醇饮食各组血清TC及ox-LDL显著升高(P均<0.01),但血清TC和ox-LDL在胆固醇组、ZnPP-IX组、血红素-L-赖氨酸盐干预组之间均无显著性差异。与对照组比较,胆固醇组主动脉CO生成量显著增加,HO-1表达升高(P均<0.01),主动脉斑块面积达(40.2±8.9)%。与胆固醇组比较,外源性血红素-L-赖氨酸盐干预组的主动脉内膜斑块面积(26.6±9.2)%明显缩小(P<0.01),主动脉HO-1表达及CO的生成量显著升高;与胆固醇组比较,血红素-L-赖氨酸盐干预组的主动脉组织内c-myc及c-fos的mRNA和蛋白表达均显著降低(P均<0.01),而ZnPP组与胆固醇组之间则无明显差异。结论HO-1/CO系统具有抗动脉粥样硬化作用,这种作用并非通过其对血浆TC及ox-LDL的调节实现,可能与该系统干预动脉组织内原癌基因表达从而抑制血管平滑肌细胞增殖有关。     

非洛地平对高胆固醇饮食载脂蛋白E基因敲除小鼠动脉粥样硬化的影响

目的：探讨钙通道阻断剂（CCB）非洛地平对载脂蛋白E基因敲除(ApoE KO)小鼠动脉粥样硬化斑块的影响。方法:ApoE KO小鼠随机分为普食组、高胆固醇饮食组、高胆固醇饮食＋非洛地平组（n=15），分别予蒸馏水或非洛地平 5 mg·kg-1·d-1灌胃12周。无创血压系统测小鼠血压；内眦动脉取血检测血清胆固醇和甘油三酯水平；冰冻切片光镜下定位主动脉根部，油红O染色评估斑块大小；实时定量PCR和Western blotting方法检测主动脉中炎症因子表达。结果:高胆固醇饮食组小鼠血脂明显升高（P<0.01），且斑块面积明显高于普食组（P<0.01）；非洛地平可以明显减小斑块面积（P<0.01），同时还可以降低肿瘤坏死因子-α（TNF-α）、单核细胞趋化因子-1 （MCP-1）和血管细胞黏附因子-1（VCAM-1）的表达。结论:钙通道阻断剂非洛地平可能通过抑制炎症反应，降低炎症因子表达，从而达到抑制动脉粥样硬化发生发展的目的。     

人冠状动脉内半乳糖凝集素3水平与斑块稳定性的相关性研究

目的:探讨人冠状动脉粥样斑块内半乳糖凝集素3(galectin-3)的表达水平与斑块结构及稳定性的关系。方法:收集尸检案例的冠状动脉标本84例,其中动脉粥样硬化但非冠心病猝死者22例(A1组),冠心病猝死但不伴有继发病变者20例(A2组),冠心病猝死且伴有继发病变者24例(A3组),无心脏疾病死亡者18例作为正常对照组(control组)。所有冠状动脉行常规HE染色检测内膜厚度、坏死核心厚度、纤维帽厚度和血管狭窄程度;以单核巨噬细胞表面标志物CD68标记病灶内的单核-巨噬细胞并计数,采用免疫组织化学、Western blot及RT-qPCR法检测冠状动脉组织中galectin-3、CD68和基质金属蛋白酶2(MMP-2)表达,并分析其表达与斑块结构及其稳定性的关系。结果:同正常组比较,病变各组粥样硬化病灶内的内膜和坏死核心增厚,纤维帽变薄,血管狭窄程度增高(P0.05);病灶内泡沫细胞数量增多(P0.05);病灶内galectin-3、CD68和MMP-2蛋白及mRNA水平较正常组显著升高,且在A1组、A2组和A3组中呈递增趋势(P0.05);病灶内galectin-3、CD68和MMP-2的表达与内膜厚度和坏死灶厚度呈正相关,与纤维帽厚度呈负相关。结论:人冠状动脉粥样硬化病灶内galectin-3表达升高,并与斑块结构稳定性相关。     

Survivin和CD44v6在子宫内膜异位症中的表达及意义

目的研究Survivin、CD44v6在卵巢子宫内膜异位症中的表达，以探讨二者与卵巢子宫内膜异位症发病的关系。方法用免疫组化S-P方法检测卵巢子宫内膜异位症31例异位内膜、5例在位内膜、15例正常内膜中Survivin和CD44v6的表达。结果Survivin蛋白在异位内膜中表达明显高于在位内膜、正常内膜（P〈0．05）；CD44v6蛋白在异位内膜组与增生期内膜比较有统计学意义（P〈0．05），与其他两组比较无统计学意义（P〉0．05）；二者的表达不随AFS分期的变化而变化；并且二者在卵巢子宫内膜异位症中的表达呈相关性（r=0．24），但无统计学意义（P〉0．05）。结论Survivin和CD44v6在卵巢子宫内膜异位症中的异常表达对卵巢子宫内膜异位症的发生及发展起着重要的作用.     

血红素氧合酶-内源性一氧化碳系统对感染性休克大鼠低血压形成的影响

目的：探讨血红素氧合酶-内源性一氧化碳系统是否参与了感染性休克大鼠低血压的形成。 方法： 将Sprague-Dawley大鼠随机分为对照（C）组、感染性休克（SS）组、感染性休克+ZnPP-IX(SZ)组、ZnPP-IX（Z）组。连续监测MAP；并检测血中COHb的浓度，主动脉和股动脉血管组织内HO-1 mRNA、HO-2 mRNA及HO-1、HO-2蛋白水平。 结果： ①SZ组大鼠其MAP水平均高于SS组(P<0.05)；②SS组大鼠主动脉和股动脉组织内HO-1 mRNA 及HO-1蛋白水平明显高于SZ组(P<0.05)，而两组主动脉和股动脉组织内HO-2 mRNA 及HO-2蛋白水平相比无显著差异(P>0.05)；③SS组大鼠血中COHb水平明显高于SZ组(P<0.05)。 结论： 感染性休克大鼠严重低血压形成的部分原因是由于HO-1蛋白水平的上调及随后的CO浓度升高所致。     

Association between the haptoglobin and heme oxygenase 1 genetic profiles and soluble CD163 in susceptibility to and severity of human malaria

Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria.     

HO-1在CCK-8减轻脂多糖所致的急性肺损伤中的作用

目的： 探讨血红素氧合酶（HO）-1在八肽胆囊收缩素（CCK-8）减轻脂多糖（LPS）所致急性肺损伤（ALI）中的作用。方法: 将大鼠随机分为5组：正常对照组、LPS组、CCK-8+LPS组、LPS+Hm（氯血红素，CO供体）组、LPS+ZnPP（锌原卟啉，HO-1特异性阻断剂）组。各组给药后2 h、6 h、12 h行支气管肺泡灌洗、检测支气管肺泡灌洗液（BALF）中中性粒细胞（PMN）数目；进行肺组织的形态学观察；测定肺组织中丙二醛（MDA）含量和HO-1蛋白活性；应用RT-PCR和Western blotting技术检测给药后6h肺组织中HO-1 mRNA和蛋白的表达情况。结果: LPS组肺组织出现损伤性变化，同时BALF中PMN数目、肺组织中MDA含量、HO-1蛋白活性、HO-1 mRNA和蛋白的表达均高于相应对照组（均P<0.05）；CCK-8+LPS和LPS+Hm组肺组织损伤程度、BALF中PMN数目和肺组织中MDA含量低于相应LPS组，而肺组织中HO-1蛋白活性、HO-1 mRNA和蛋白的表达均高于相应LPS组（均P<0.05）；LPS+ZnPP组肺组织损伤程度、BALF中PMN数目和肺组织中MDA含量分别高于相应LPS组，而肺组织中HO-1蛋白活性、HO-1 mRNA和蛋白的表达分别低于相应LPS组（均P<0.05）。结论: CCK-8可部分通过HO-1介导的抗氧化、抑制PMN聚集等效应来发挥减轻LPS所致的肺损伤作用。     

Erythrocyte Fragment Count Predicts Hemolysis in Roller Pumps

Objective： Hemolysis in blood pumps has been measured by various in vitro test methods, in which normalized index of hemolysis （NIH） was established. As NIH is complicated and difficult to calculate, erythrocyte fragment count is proposed in the present study to predict hemolysis in roller pumps. Methods： Five paired in vitro tests were conducted using the POLYSTAN pediatric pump（group A） and COBE pump（ group B）. Ten whole blood samples （400 ml ） were circled in the roller pump for 16 h. Erythrocyte fragments count and plasma-free hemoglobin （FHb） were measured before pumping and every two hours through circulation after four-hour-pumping. The morphological changes of erythrocyte were observed by scanning electron microscope. Results： The two groups＇ EFC and FHb levels were increased linearly during a long duration of pumping and linear regression of erythrocyte fragments count and plasma-free hemoglobin were correlated. Conclusion： Erythrocyte fragments count could be used as an index in evaluating the in vitro hemolytic properties of blood pumps.     

血细胞碎片计数评价滚压泵溶血的意义

探讨血细胞碎片计数在血泵离体实验中的意义.分别采用POLYSTAN和COBE滚压泵,对血样本各作5次16 h离体长时间转流实验.转流前血样本作对照组、转流后4 h第1次抽取血标本,以后每隔2 h抽取1次血标本.检测指标:血细胞碎片计数、游离血红蛋白和红细胞形态学电镜观察.结果发现:分别用两种滚压泵转流后,血细胞碎片计数值均随转流时间延长而呈线性逐渐增加,各时点值与前一时点相比,有显著差异(P＜0.05).两组游离血红蛋白量也随转流时间延长而呈线性增加.血细胞碎片计数与游离血红蛋白呈直线回归相关关系.红细胞形态学电镜观察亦表明,转流时间越长,红细胞损伤越严重.实验结果提示,在滚压式血泵离体转流实验中,血细胞碎片计数可以作为一项评价血泵离体溶血性能的方便、客观指标.     

Heme Oxygenase-1 expression in M-CSF-polarized M2 macrophages contributes to LPS-induced IL-10 release

The shift between pro-inflammatory (M1) and anti-inflammatory (M2) states of macrophage polarization allows the resolution of inflammatory processes as well as the maintenance of a basal anti-inflammatory environment in tissues continuously exposed to harmless antigens (e.g., lung and gut). To identify markers for the anti-inflammatory state of macrophages, expression profiling was performed on human macrophages polarized by either GM-CSF or M-CSF, which lead to the generation of TNF-α and IL-12p40-producing pro-inflammatory macrophages [M1 (GM-CSF)] or IL-10-producing anti-inflammatory macrophages [M2 (M-CSF)] upon exposure to LPS, respectively. A different iron metabolism gene signature was detected in both macrophage types, with the heme regulatory molecules CD163 and Heme Oxygenase-1 (HO-1) being preferentially expressed by M2 (M-CSF) macrophages. M1-polarizing cytokines (GM-CSF, IFNγ) inhibited, while IL-4 enhanced, the M-CSF-driven HO-1 expression. In agreement with this in vitro data, HO-1 expression in metastatic melanoma was primarily detected in CD163⁺ tumor-associated macrophages, which are known to exhibit an M2-skewed polarization phenotype. In contrast to the HO-1 inhibitor tin protoporphyrin (SnPP), the administration of cobalt protoporphyrin (CoPP), a potent inducer of HO-1 resulted in increased LPS-triggered IL-10 release from M2 (M-CSF) macrophages. The data suggests that HO-1 is important for the anti-inflammatory activities of M-CSF-polarized M2 macrophages. Moreover, since M2 (M-CSF) macrophages also express higher levels of the CD163 scavenger receptor, the CD163/HO-1/IL-10 axis appears to contribute to the generation of an immunosuppressive environment within the tumor stroma.     

Clinical significance of M2 macrophages expressing heme oxygenase-1 in malignant transformation of ovarian endometrioma

Malignant transformation of endometriosis is a rare and still poorly understood event, but is associated with the distortion of the pro-oxidant and anti-oxidant balance. The aim of the present study was to quantify the numbers of macrophages polarized as M1 or M2 phenotypes and the expression of heme oxygenase (HO)-1 in tissue sections from patients with benign ovarian endometrioma (OE) and its malignant transformation (endometriosis-associated ovarian cancer, EAOC). We performed a retrospective study at the Department of Gynecology, Nara Medical University hospital from December 2012 to March 2015. This study included 53 patients with OE (n?=?33) and EAOC (n?=?20), and we evaluated polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c, CD163 and HO-1. The number of the M1 phenotype (CD11c⁺, p?=?0.001) and the M2 phenotype (CD163⁺, p?=?0.009) was significantly lower in EAOC patients than in OE patients. Analyzing the correlations between the studied markers, the expression of CD68, CD11c, and CD163 proteins significantly correlated with each other (p?<?0.001). The number of M2 phenotypes expressing HO-1 was significantly decreased in the EAOC group, compared with the OE group (P?<?0.001), demonstrating sustained downregulation of an antioxidant marker, HO-1, in EAOC. In conclusion, reduced number of M2 macrophages expressing HO-1 may have an important role in promoting malignant transformation of OE.     

滚压泵离体长时间转流对红细胞损伤的研究

目的 :探讨滚压泵长时间转流对红细胞的损伤。方法 :采用两种滚压泵Polystan小儿泵 (A组 )和COBE泵 (B组 )分两组 ,作 5对 16h离体转流实验。测定项目 :FHb、PLT、红细胞脆性度、红细胞电镜扫描观察。血标本为转前、转中 4h后每隔 2h抽血标本 ;电镜标本为转前、转中每隔 4h抽一次。结果 :1.FHb随转流时间延长而呈线性增加 ,两组溶血指数分别为 0 .2 96mg/L/h和 0 .3993mg/L/h。两组没有差异 ;2 .PLT同FHb一样呈线性增加 ,直线回归分析提示 ,二者有明显的相关性 ;3.两组红细胞脆性度转中无明显改变 ;4 .电镜观察显示 ,转中标本可见到各种变形红细胞膜 ,棘球红细胞计数表明 ,转流时间越长 ,棘球红细胞数越多。结果 1.滚压泵长时间转流不但使部分红细胞直接破损 ,引起即时溶血 ,而且还造成大量红细胞亚损伤 ,导致术后的延迟性溶血 ;2 .红细胞形态学的改变是导致术后延迟性溶血的基础。     

Blood-brain barrier disruption and oxidative stress in guinea pig after systemic exposure to modified cell-free hemoglobin

Systemic exposure to cell-free hemoglobin (Hb) or its breakdown products after hemolysis or with the use of Hb-based oxygen therapeutics may alter the function and integrity of the blood-brain barrier. Using a guinea pig exchange transfusion model, we investigated the effect of a polymerized cell-free Hb (HbG) on the expression of endothelial tight junction proteins (zonula occludens 1, claudin-5, and occludin), astrocyte activation, IgG extravasation, heme oxygenase (HO), iron deposition, oxidative end products (4-hydroxynonenal adducts and 8-hydroxydeoxyguanosine), and apoptosis (cleaved caspase 3). Reduced zonula occludens 1 expression was observed after HbG transfusion as evidenced by Western blot and confocal microscopy. Claudin-5 distribution was altered in small- to medium-sized vessels. However, total expression of claudin-5 and occludin remained unchanged except for a notable increase in occludin 72 hours after HbG transfusion. HbG-transfused animals also showed increased astrocytic glial fibrillary acidic protein expression and IgG extravasation after 72 hours. Increased HO activity and HO-1 expression with prominent enhancement of HO-1 immunoreactivity in CD163-expressing perivascular cells and infiltrating monocytes/macrophages were also observed. Consistent with oxidative stress, HbG increased iron deposition, 4-hydroxynonenal and 8-hydroxydeoxyguanosine immunoreactivity, and cleaved caspase-3 expression. Systemic exposure to an extracellular Hb triggers blood-brain barrier disruption and oxidative stress, which may have important implications for the use of Hb-based therapeutics and may provide indirect insight on the central nervous system vasculopathies associated with excessive hemolysis.     

HO-1/CO径路在肺缺血-再灌注损伤中的作用

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1 h、2 h、3 h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。