丙泊酚对急性肺损伤大鼠血红素氧合酶-1表达的影响

目的探讨丙泊酚对肺的保护作用及其可能作用机制。方法通过尾静脉注射内毒素建立急性肺损伤模型,丙泊酚和锌原卟啉同样经过尾静脉给药。将Wistar大鼠随机分入实验对照组（C组）、脂多糖组（L组）、脂多糖＋丙泊酚组（LP组）和锌原卟啉组（LZ组）。给药前及开始后第3、6和12h测定动脉血氧分压（PaO2）,实验结束后观察肺湿/干重（W/D）比值、肺组织病理学检查并进行肺损伤轻重程度评分,同时观察各组大鼠肺组织血红素氧合酶-1（HO-1）含量。结果实验前各组PaO2无明显差异,注射LPS后L组PaO2持续下降,和C组相比其PaO2显著降低（P〈0.05）。实验结束后L组和C组相比其W/D比值、肺组织病理学检查评分及HO-1含量显著增加（P〈0.05）。而LP组和L组相比W/D比值、肺组织病理学检查评分含量显著降低（P〈0.05）,而PaO2和HO-1含量显著升高（P〈0.05）。而LZ组加入锌原卟啉后明显抑制丙泊酚以上保护作用。结论丙泊酚具有肺保护作用,且该作用可能与其通过增加HO-1表达作用相关。     

人血红素氧合酶-1重组腺病毒的构建与鉴定

目的构建人血红素氧合酶-1(hHO-1)重组腺病毒,用以对供体器官的预处理。方法将人hHO-1cDNA克隆于腺病毒穿梭质粒pSGCMV,得到重组质粒pSGCMV-hHO-1。采用位点特异性重组系统(Cre/Loxp)将pSGCMV-hHO-1与腺病毒骨架载体pBHGloxP△E3通过lipofectamine2000共转染至293细胞,生成带有hHO-1基因的重组腺病毒载体Ad-hHO-1。重组腺病毒质粒在293细胞中扩增,CsCl梯度离心纯化。结果经酶切鉴定和测序证实载体构建的正确性,病毒滴度为2.0×1010pfu/ml。结论成功构建带有hHO-1cDNA的重组腺病毒,用以器官移植时缺血再灌注损伤的基因治疗。     

血红素氧合酶-1对急性呼吸窘迫综合征大鼠的防治作用

血红素氧合酶 (hemeoxygenase ,HO)是一种催化血红素降解为一氧化碳、铁和胆红素的起始酶和限速酶 ,有着重要的生物学作用[1] 。故已逐渐成为目前研究的一个热点[2 4] 。本实验拟以油酸型急性呼吸窘迫综合征 (ARDS)大鼠为模型 ,先用HO 1的作用底物—血红蛋白 (Hb)来诱导HO 1的     

血红素氧合酶-1的表达水平同冠心病的相关性分析

目的探讨血红素氧合酶-1(HO-1)的表达水平与冠心病的相关性。方法急性心肌梗死(AMI)组32例,稳定型心绞痛(AP)组35例,不稳定型心绞痛(UAP)组31例,体检不存在心脑血管疾病患者40例列入对照组,分析4组HO-1表达水平。结果各组冠心病患者HO-1表达水平与对照组存在明显差异(P<0.05),随着患病程度的减轻,HO-1表达平均面积、绝对灰度和蛋白带灰度峰值逐渐降低(P<0.05)。结论 HO-1的表达水平与冠心病的程度密切相关,随着粥样斑块的破裂和血栓的形成,氧化应激反应逐渐加重,HO-1呈现出越来越高的表达。     

稽留流产患者血清中缺氧诱导因子-1α、血红素氧合酶-1及14-3-3β的表达及临床意义

目的 检测稽留流产患者血清中缺氧诱导因子-1α(HIF-1α)、血红素氧合酶-1(HO-1)及14-3-3β的表达情况,并探讨其临床意义.方法 收集2019年1-12月高安市人民医院妇科住院部收治的稽留流产患者的血清标本74例,设为实验组;同期正常宫内早孕要求终止妊娠的患者血清标本58例,设为对照组.运用酶联免疫吸附法...     

乌司他丁对老年患者上腹部手术后血红素氧合酶-1与细胞因子的影响

目的 探讨乌司他丁（UTI ）对老年患者上腹部手术后血红素氧合酶-1 （HO-1）活性和细胞因子变化的影响. 方法 择期行上腹部手术老年患者40例,随机分为两组（n＝20）. 试验组给予乌司他丁 1万U&#8226;kg^-1; 对照组给予等容积0.9%氯化钠注射液. 乌司他丁给药方法 ：患者入室开放中心静脉,随即开始采用微量泵快速泵入乌司他丁,于切皮前泵入总量1/3（约30 min）,余2/3维持至手术结束. 分别于中心静脉开放后即刻（t₀）、术毕（t ₁）、术后6 h（t ₂）、术后12 h（t ₃）、术后24 h（t ₄）时点取中心静脉血检测血清肿瘤坏死因子（ TNF-α）、白细胞介素-6（IL-6）及HO-1,并行统计学分析. 结果 与t ₀点比较,对照组HO-1活性t ₃时开始升高,t ₄时达峰值（P＜0.05）,IL－6浓度术后各时点均升高,t ₂时达高峰 （P＜0.05）,TNF－α浓度术后各时点均升高,t ₃时达峰值呈进行性升高（ P＜0.05）;与对照组比较,试验组HO-1活性t ₄时升高（P＜0.05）, IL-6浓度t ₁～ t ₄时均降低（P＜0.05）,TNF-α浓度t ₂～ t ₄时降低 （P＜0.05）. 结论 老年患者上腹部手术后TNF-α、IL-6浓度及HO-1活性明显升高,乌司他丁能明显减少老年人上腹部手术后血清细胞因子TNF-α、 IL-6的释放,促进血清HO-1活性升高.     

血红素氧合酶1基因对高血糖和波动性高血糖诱导血管内皮细胞凋亡的影响

目的探讨血红素氧合酶1对高血糖和波动性高血糖诱导内皮细胞凋亡的影响。方法以未转染及转染血红素氧合酶1基因的人脐静脉内皮细胞为研究对象,实验分正常葡萄糖组、波动性高血糖组、正常葡萄糖／血红素氧合酶l组、稳定性高血糖／血红素氧合酶1组及波动性高血糖／血红素氧合酶1组。细胞分别置于含正常浓度葡萄糖（5．5mmol／L）、稳定性高浓度葡萄糖（20．0mmol／L）和波动性高浓度葡萄糖（5．5或20．0mmol／L）的培养基,培养7d后用噻唑蓝（MTF）方法检测细胞存活率,吖啶橙／溴乙啶（AO／EB）染色法检测细胞凋亡,逆转录-聚合酶链反应（RT-PCR）检测凋亡相关基因bax、bel-2mRNA的表达。结果转染内皮细胞血红素氧合酶1mRNA表达量明显高于未转染内皮细胞[（0．91±0．29）比（0．43±0．14）,P〈0．05]。正常葡萄糖组、止常葡萄N／血红素氧合酶1组、稳定性高血糖组、稳定性高血糖／血红素氧合酶1组、波动性高血糖组、波动性高血糖／血红素氧合酶1组细胞存活率分别为（100±22）％、（110±19）％、（79±11）％、（108±27）％、（59±13）％、（87±9）％,凋亡细胞数分别为（33±7）、（32±7）、（53±5）、（35±7）、（59±7）、（48±7）。稳定性高血糖组和波动性高血糖组细胞存活率较正常葡萄糖组明显下降（P〈0．05或P〈0．01）,且波动性高血糖组细胞存活率下降更为明显（P〈0．05）;稳定性高血糖／血红素氧合酶组及波动足性高血糖／血红素氧合酶组细胞存活率较稳定性高血糖组及波动性高向．糖组均提高（P〈0．05）。止常葡萄精组、正常葡萄糖／血红素氧合酶1组、稳定性高血糖组、稳定性高咀糖／血红素氧合酶1组、波动性高血糖组、波动性高血糖／血红素氧合酶l组bax／β-actin表达分别为（1．27±0．32）、（1．26±0．35）、（1．13±0．32）、（1．13±0．39）、（1．32±0．45）、（1．31±0．41）,bcl-2／β-actin表达分别为（1．35±0．39）、（1．31±0．34）、（0．77±0．35）、（1．34±0．46）、（0．20±0．12）、（0．82±0．23）。稳定性高血糖组与波动性高血糖组bcl-2的表达比止常葡萄精组明显减弱（P〈0．05或P〈0．01）,与稳定性高血糖组和波动性高血糖组相比,稳定性高血糖／血红素氧合酶1组、波动性高血糖／血红素氧合酶1组bcl-2mRNA表达增强（P〈0．01）。结论血红素氧合酶1基因的表达上调可减轻高血糖和波动性高血精引起的血管内皮细胞凋广,其机制与bcl-2的表达上调有关。     

克拉霉素对哮喘大鼠肺组织血红素氧合酶-1的调控

目的:研究哮喘大鼠肺组织中血红素氧合酶-1(HO-1)的表达情况及克拉霉素对HO-1的调控作用;观察其HO-1表达与BALF中EOS占细胞总数的百分比(EOS%)、嗜酸性粒细胞(EOS)、全血COHb的百分比含量之间的相关性。方法:清洁级雄性SD大鼠30只,随机分为正常对照组(N组)、哮喘组(A组)、克拉霉素治疗组(C组),每组10只。测定全血COHb的百分比含量;计数BALF沉渣中细胞总数和分类;计数肺组织中浸润的炎性细胞数;免疫组织化学染色法观察HO-1在哮喘大鼠肺组织的表达。结果:HO-1主要表达在气道上皮细胞,三组HO-1阳性表达的平均吸光度分别为0.07±0.01、0.22±0.03、0.14±0.02。A组HO-1表达水平显著高于N组(P<0.001),C组HO-1蛋白的表达显著低于A组(P<0.01)。HO-1表达水平与全血COHb的百分比含量、BALF中EOS占细胞总数的百分比及肺组织中EOS总数均呈显著正相关(分别为r=0.887,P<0.01;r=0.889,P<0.01;r=0.883,P<0.01)。结论:哮喘大鼠的肺组织HO-1表达水平显著增加,提示HO-1可能参与哮喘发病过程。克拉霉素明显改善哮喘的气道炎症浸润,其作用机制部分是通过抑制HO-1起作用。     

血红素氧合酶-1与心肌肥厚

血红素氧合酶-1（heineoxygenase-1，HO-1）是哺乳动物中血红素代谢的限速酶。越来越多的研究发现HO-1及其催化代谢产物通过各种途径在心血管疾病中发挥着抗炎、抗氧化、抗增殖、抑制凋亡、抑制血小板凝集、细胞保护及调节血管张力等许多重要生物学作用。近年来发现HO—1具有抗心肌肥厚的作用，现就HO-1与心肌肥厚的研究进展作一综述。     

阿托伐他汀钙对脂多糖诱导急性肺损伤小鼠核因子E2相关因子2/血红素加氧酶-1通路的影响

目的 探讨阿托伐他汀钙(AVT)对脂多糖(LPS)诱导急性肺损伤(ALI)小鼠核因子E2相关因子2/血红素加氧酶-1(Nrf2/HO-1)通路的影响。方法 2021年9―12月,采用随机数字表法把15只BALB/c雌性小鼠分为NS组(尾静脉注射生理盐水)、LPS组(尾静脉注射LPS诱导ALI模型)、LPS+AVT组(经AVT灌胃治疗的ALI模型),每组各5只。收集动脉血,测定血氧分压(PaO₂)、氧合指数(PaO₂/FiO₂);处死后取出双肺,HE染色观察肺组织,测定湿干重比(W/D),酶联免疫吸附(ELISA)法测肺泡灌洗液(BALF)中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量,蛋白质印迹法(Western blotting)测肺组织中Nrf2、HO-1的表达。结果 NS组、LPS组及LPS+AVT组PaO₂ [(89.66±8.54)、(50.88±6.26)、(67.84±5.76)mmHg]、PaO₂/FiO₂[(426....     

Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1

Clinical trials with partial liquid ventilation demonstrate improvement in oxygenation, as well as some adverse side effects linked to the application of liquid perfluorocarbons (PFCs) during liquid ventilation. Thus, we examined the effects of systemic administration of PFC on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its effects on heme oxygenase-1 (HO-1), a compound that provides potent cytoprotection against lung injury.Rats were assigned to one of six groups (n = 8). Thirty minutes after they were challenged with LPS aerosol inhalation, perfluorohexane was given intraperitoneally every two hours. Ten hours after LPS inhalation, bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for enzyme linked immunosorbent assay, histologic, and Western-blot analyses. The results showed that perfluorohexane significantly decreased the wet to dry weight ratio, malondialdehyde (MDA) production, and myeloperoxidase (MPO) activity in the lung tissue. Also, perfluorohexane reduced the total protein content and levels of tumor necrosis factor-α (TNF-α) but increased the levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in the BALF, resulting in decreased pulmonary edema and the infiltration of neutrophils into the lung tissues of LPS-treated rats. Furthermore, perfluorohexane increased HO-1 protein production and stimulated HO-1 activity in the lung tissue. Pre-treatment with Zinc protoporphyrin IX, an inhibitor of HO-1, decreased the protective effects of perfluorohexane in rats.In summary, systemic perfluorohexane alleviates LPS-induced lung injury in rats, and HO-1 may be involved in the mechanism of this reduction.     

辛伐他汀对急性心肌梗死大鼠血红素加氧酶-1的影响

目的探讨大鼠急性心肌梗死后心肌内血红素加氧酶-1(HO-1)水平变化及辛伐他汀对HO-1表达的影响。方法结扎♂SD大鼠冠状动脉左前降支建立心肌梗死模型,24 h后存活大鼠随机分为心肌梗死组(MI组)、辛伐他汀(Sim组)和假手术组(Sham组,只穿线不结扎)。Sim组以辛伐他汀40 mg.kg-1.d-1灌胃,MI组和Sham组以等体积生理盐水灌胃。术后24 h、7 d、28 d处死动物,RT-PCR及Western bolt测定心肌非梗死区HO-1 mRNA和蛋白表达水平,并测非梗死区心肌超氧化物岐化酶(SOD)活性、丙二醛(MDA)含量。结果HO-1 mRNA和蛋白表达水平均在心梗后24 h开始升高,7 d达峰,28 d恢复至基线水平。3个时间点MI组上述指标均高于Sham组;术后7 d和28 d Sim组上述指标均高于MI组(P<0.05)。随HO-1 mRNA和蛋白表达水平升高,SOD活性升高,MDA含量降低。结论心肌内HO-1水平在急性心肌梗死后28 d内呈现动态变化。辛伐他汀可诱导HO-1表达,发挥抗氧化损伤的心脏保护作用。     

Propofol attenuation of renal ischemia/reperfusion injury involves heme oxygenase-1

Aim： To examine the protective effect of propofol in renal ischemia/reperfusion （I/R） injury and the role of heme oxygenase-1 （HO-1） in this process. Methods： Sprague-Dawley rats were randomly divided into 3 groups： （i） sham-operated group; （ii） I/R group; and （iii） propofol group. Bilateral renal warm ischemia for 45 min was performed. After 2, 6, and 24 h reperfusion, blood samples and kidneys were collected for assessment of renal injury, and HO-1 expressions were analyzed by immunohistochemical analysis, RT-PCR and Western blotting. Results： Blood urea nitrogen and serum creatinine levels in the propofol group were significantly lower than that in the I/R group at 24 h after reperfusion. The mean histological score by Paller＇s standard showed that propofol significantly attenuated renal I/R injury after 6 h reperfusion. Propofol increased HO-1 mRNA and protein levels 2 h after reperfusion, whereas HO-1 expressions were present at exceedingly low levels in the I/R group and the sham-operated group at same time point. Propofol also markedly increased HO-1 mRNA and protein levels than I/R at 6 and 24 h after reperfusion. Conclusion： These results suggest that propofol mitigates renal I/R injury in rats. This protection may be partly through the induction of the HO- 1 expression.     

血红素加氧酶-1的表达对实验性肝硬化内毒素血症大鼠的影响

目的:探讨血红素加氧酶-1(HO-1)的表达对实验性肝硬化内毒素血症大鼠的影响。方法:32只健康雄性wistar大鼠,随机分为4组,正常+脂多糖(LPS)(对照组)、肝硬化+生理盐水对照组(TAA组)、肝硬化+LPS组(TAA+LPS组)、肝硬化+LPS+hemin(氯化高铁血红素)(HM组)。用硫代乙酰胺(TAA)诱导肝硬化模型时间共计10周,对照组自由饮清水。于模型造成后,向对照组、TAA+LPS组、HM组大鼠腹腔内注入LPS3 mg/kg;TAA组大鼠腹腔内注入等量的生理盐水;HM组于注射LPS 12 h前,腹腔注射HM(40 mg/kg),并在注入LPS 6 h后,各组动物经腹主动脉穿刺采全血观察血浆中丙氨酸氨基转移酶(ALT)、天门冬氨基酸转移酶(AST)、一氧化氮(NO)及丙二醛(MDA)的表达。留肝组织用免疫组织化学法观察HO-1的表达。结果:对照组、TAA组、TAA+LPS组、HM组血浆中的ALT/AST、MDA、NO依次升高差异有显著性(P<0.05),对照组、TAA、TAA+LPS、HM组各组大鼠的灰阶值显著依次降低,且有明显差别(P<0.05)。结论:在实验性的肝硬化内毒素中尽管HO-1的表达增加,但它未起到保护作用,它与内毒素对机体的损伤有关。     

姜黄素对急性肺栓塞大鼠氧化损伤及血红素加氧酶-1表达的影响

目的观察姜黄素对急性肺栓塞大鼠氧化损伤的作用及对血红素加氧酶-1(HO-1)表达的影响。方法大鼠分为假手术组、模型组、姜黄素低、高剂量(50 mg/kg、150 mg/kg)组。制备急性自体血栓肺栓塞模型。进行血气分析。检测肺组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性、丙二醛(MDA)含量;HE染色观察肺组织病理改变;RT-PCR方法和Western blot法检测肺组织HO-1的表达。结果与模型组比较,姜黄素低、高剂量组可不同程度的升高PO2、PCO2水平,升高SOD、GSH-Px、CAT活性,降低MDA含量,减轻肺组织的氧化病理损伤。姜黄素低、高剂量组均能显著升高肺组织HO-1表达。结论姜黄素对急性肺栓塞大鼠有抗氧化损伤作用,并能上调肺组织HO-1表达。     

血红素加氧酶-1重组乳酸乳球菌灌胃对内毒素血症大鼠肠道的保护作用

目的利用基因工程原理合成携带血红素加氧酶-1(HO-1)基因的乳酸乳球菌,通过对正常大鼠灌胃后,观察其是否有对内毒素血症大鼠肠道肠粘膜保护效应,及减轻肠道炎症反应。方法将24只健康清洁级♂SD大鼠随机分为携带HO-1基因的乳酸乳球菌灌胃组(HO-1组,n=8)、乳酸乳球菌灌胃组(LL组,n=8)、谷氨酰胺灌胃组(Glu组,n=8)。分别给予携带HO-1基因的乳酸乳球菌、乳酸乳球菌或谷氨酰胺,每日1次,共4次。d4腹腔内注射内毒素,12h后取末端回肠。比较各组动物的死亡率,检查肠组织病理学变化,并检测肠组织髓过氧化物酶(MPO)活性、肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)含量和血红素加氧酶-1(HO-1)的表达量。结果与LL组比较,HO-1组的生存率均明显升高(P<0.05);HO-1组和Glu组chiu′s评分和肠组织MPO活性明显降低(均P<0.01);肠组织TNF-α的含量明显减低(P<0.01),IL-10的含量却明显升高(P<0.01);HO-1的含量明显增加(P<0.01);与Glu组比较,HO-1组的IL-10的含量和HO-1的含量明显增加(P<0.01,P<0.05)。结论携带HO-1基因的乳酸乳球菌对内毒素血症大鼠肠粘膜有较好的保护作用,且能明显减轻肠道炎症反应。     

诱导血红素氧化酶-1表达的化合物研究进展

血红素氧化酶-1(HO-1)是一种细胞应激性蛋白，它的表达在许多病理和生理过程中起着重要的调节作用。虽然它在机体多数组织中表达水平低或不表达，但大量的临床和药理实验证明很多化合物可通过调节不同的转录因子和信号传导途径而诱导HO-1表达，从而发挥一定的疗效。本文总结了近十年来该领域国内外研究的几类化合物，并对其诱导机制进行简要分析。     

Effects of induction/inhibition of endogenous heme oxygenase-1 on lipid metabolism, endothelial function, and atherosclerosis in rabbits on a high fat diet

The heme oxygenase-1 (HO-1) / carbon monoxide (CO) system has been presumed as a therapeutic target for preventing atherosclerosis. However, the exact mechanism(s) underlying this system remains largely undefined. This study aims to examine the influence of induction/inhibition of HO-1 on atherosclerotic plaque using pharmacological approaches and to elucidate potential mechanisms. Rabbits were randomly assigned to receive a standard diet (control group), high fat diet (HFD), HFD plus HO inducer hemin (HFD + H group), and HFD plus an HO inhibitor, zinc protoporphyrin-9 (ZnPP9, HFD + Z group). Atherosclerotic plaque was evaluated using oil red O staining and histological analyses. Immunohistochemistry, western blotting, and RT-PCR were employed to study the expression of HO-1 and endothelin-1 (ET-1). Levels of CO, nitric oxide (NO), eNOS/iNOS activities, NF-κB activity, and TNF-α level were determined. No significant differences of serum lipid levels were observed among the HFD, HFD + Z, and HFD + H groups. In rabbits, HFD induced typical atherosclerotic plaque and increased intima/media thickness ratio, which was markedly reduced in the HFD + H group and further aggravated in the HFD + Z group. Furthermore, hemin increased HO-1 expression, CO levels, and eNOS activity, while decreasing iNOS levels, ET-1 expression, NF-κB activity, and TNF-α level. ZnPP9 caused opposite effects. Induction of the endogenous HO-1/CO system by hemin can prevent atherosclerosis though increasing CO levels, regulating eNOS activity, NF-κB activity, TNF-α levels, and ET-1 levels in rabbits. Our results add new evidence for the importance of HO-1 in the genesis and development of atherosclerosis and provide several possible mechanisms underlying the anti-atherosclerosis effects of HO-1.     

Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1.

Curcumin (diferuloymethane), a yellow colouring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), has been reported to possess anti-inflammatory, antioxidant, antimutagenic and anticarcinogenic activities. Curcumin exerts its chemoprotective and chemopreventive effects via multiple mechanisms. It has been reported to induce expression of the antioxidant enzymes in various cell lines. Heme oxygenase-1 (HO-1) is an important antioxidant enzyme that plays a pivotal role in cytoprotection against noxious stimuli of both endogenous and exogenous origin. In the present study, we found that oral administration of curcumin at 200mg/kg dose for four consecutive days not only protected against dimethylnitrosamine (DMN)-induced hepatic injury, but also resulted in more than three-fold induction of HO-1 protein expression as well as activity in rat liver. Inhibition of HO-1 activity by zinc protoporphyrin-IX abrogated the hepatoprotective effect of curcumin against DMN toxicity. NF-E2-related factor 2 (Nrf2) plays a role in the cellular protection against oxidative stress through antioxidant response element (ARE)-directed induction of several phase-2 detoxifying and antioxidant enzymes including HO-1. Curcumin administration resulted in enhanced nuclear translocation and ARE-binding of Nrf2. Taken together, these findings suggest that curcumin protects against DMN-induced hepatotoxicity, at least in part, through ARE-driven induction of HO-1 expression.