大鼠耐力训练增加血红素加氧酶1诱导的血管舒张

目的观察大鼠急性耐力训练运动后血管收缩及舒张功能的变化并探讨其机制。方法健康雄性SD大鼠在运动平板上进行跑步适应性训练2周后,进行一周耐力训练。训练方式为平板跑,运动5d/周,耐力训练时平均运动距离2000~2300m/d。同年龄安静饲养动物为对照。运动结束时取降主动脉在体外检测血管对80mmol/L高钾溶液与1μmol/L苯肾上腺素的收缩反应,以及血管对乙酰胆碱的舒张反应。阻断一氧化氮合酶(NOS)及血红素加氧酶1(HO-1)后再次观察血管对乙酰胆碱的舒张反应。部分主动脉环进行免疫组织化学检测血管内皮HO-1。同年龄静止饲养大鼠作为对照。结果大鼠经1周耐力运动训练后,主动脉对高钾溶液的收缩反应未见明显变化,对苯肾上腺素引起的收缩反应显著减弱,对乙酰胆碱的舒张反应显著增强(P<0.01)。NOS阻断剂预孵后,正常不运动对照大鼠血管内皮依赖性舒张被阻断达(97.7±3.3)%,经过耐力训练的大鼠血管被阻断(78.8±2.1)%(与对照组比较,P<0.01),耐力训练组尚存的内皮依赖性舒张可被HO-1阻断剂proto-porphyrin IX Zinc(Ⅱ)进一步阻断。免疫组化结果显示主动脉血管HO-1显著增加。结论急性耐力运动训练后血管内皮依赖性舒张功能增强,该作用可能与运动诱导的血管内皮中HO-1增加有关。     

不同HO-1表达水平对糖尿病模型大鼠血管舒张功能及NOS的影响

目的 探讨改变血红素加氧酶-1(HO-1)表达水平对糖尿病(DM)大鼠血管舒张功能的影响及与一氧化氮合酶(NOS)/一氧化氮(NO)的关系.方法 以链脲佐菌素(STZ)诱导DM大鼠模型.SD大鼠分成4组:对照组、DM组、正铁血红素(HO-1诱导剂)组、锌原卟啉(HO-1抑制剂)组.应用离体血管张力检测技术观察胸主动脉舒张功能变化;RT-PCR法及比色法分别检测血管组织和血清中诱生型NOS(iNOS)及内皮型NOS(eNOS)的表达和NO含量.结果 与DM组相比,正铁血红素组血管环对乙酰胆碱舒张百分率有所提高,而锌原卟啉组血管舒张反应继续下降.应用正铁血红素可在提高DM大鼠血管和血清eNOS表达的同时降低iNOS/NO表达;而锌原卟啉组血清中iNOS活性及其在血管组织表达均增高.结论 提高HO-1的表达水平有益于改善DM大鼠血管舒张反应失调,这种保护作用与抑制iNOS/NO的生成、上调eNOS表达水平有关.     

血红素加氧酶和一氧化氮合酶在缺血性脑损伤时的保护作用

内源性一氧化氮(NO)和一氧化碳(CO)是先后发现的2种气体信号分子,NO合酶(NOS)和血红素加氧酶(HO)分别是生成NO和CO的氧合酶。研究表明,NOS/NO系统和HO/CO系统均与缺血性脑损伤的发生发展密切相关,而且两者之间还存在着错综复杂的相互作用,对其作用机制的深入了解有助于探索缺血性脑损伤的临床治疗途径。     

血红素加氧酶-1在糖尿病大鼠心肺、血管组织的表达

目的观察和比较糖尿病大鼠血管、心脏和肺脏组织中血红素加氧酶-1(HO-1)表达水平。方法应用RT-PCR和免疫组织化学技术检测链脲佐菌素诱导的糖尿病大鼠心脏、肺脏和胸主动脉HO-1mRNA和蛋白的表达。结果与对照组相比,糖尿病大鼠心脏和肺脏组织的HO-1表达增强,而胸主动脉HO-1表达无差异。结论与心脏、肺脏相比较,血管组织不能在糖尿病状态下有效表达HO-1。     

血红素加氧酶-1对糖尿病大鼠胸主动脉功能的影响

目的探讨血红素加氧酶-1（HO-1）对糖尿病（DM）大鼠大血管功能的影响。方法SD大鼠分为4组：对照组、DM组、hemin（HO-1诱导剂）＋DM组、锌原卟啉（ZnPP,HO-1抑制剂）＋DM组。RT-PCR法检测血管组织HO-1表达水平 应用离体血管张力检测技术观察胸主动脉血管的反应性 扫描电镜下观察血管内皮超微结构。结果hemin＋DM组HO-1mRNA水平是对照组的2.01倍。与DM组相比,hemin＋DM组血管环对乙酰胆碱（Ach）舒张百分率增高,对苯肾上腺素（PE）的收缩反应减弱,内皮细胞形态有所改善 而ZnPP＋DM组大鼠对Ach的舒张反应继续下降,内皮细胞破坏严重。结论提高HO-1的表达水平有益于改善DM大鼠大血管反应性失调。     

血红素加氧酶-1对慢性肾功能衰竭大鼠高血压的影响

目的 建立大鼠慢性肾功能衰竭高血压模型，研究血红素加氧酶-1(HO-1)对慢性肾功能衰竭大鼠血压的影响，并探讨血红素加氧酶-1在慢性肾衰血压调节中的作用和机制。方法 5／6肾切除法建立慢性肾功能衰竭，大鼠随机分成3组：①正常组，②肾衰组，③Hemin组(肾衰 HO-1诱导剂组)。检测术后第6、8、10周的血压，第10周血清尿素氮、肌酐、血浆和肾组织丙二醛(MDA)，双波长分光光度法测量血浆内源性CO的水平，观察第10周肾脏病理改变，免疫组织化学方法检测肾组织HO-1的表达，应用RT-PCR和Western Blot检测肾组织HO-1 mRNA和蛋白质的表达。结果 诱导慢性肾功能衰竭大鼠体内HO-1表达可以：①明显升高血浆内源性CO水平(P＜0．05)；②减少血浆和肾组织MDA；③明显降低慢性肾功能衰竭大鼠血压(P＜0．01)；④降低血清尿素氮、肌酐(P＜0．01)；⑤减轻肾小球系膜增生、间质损害。结论 HO-1可以通过释放内源性CO和减少血浆氧化应激水平而降低慢性肾衰大鼠血压，此外它还可能具有降压效应以外的肾脏保护作用。     

精氨酸残基和赖氨酸残基对大鼠血红素加氧酶-1催化功能的影响

目的研究和探讨大鼠血红素加氧酶-1(RHO-1)中保守的碱性氨基酸精氨酸残基和赖氨酸残基对该酶催化功能的影响。方法应用定点诱变制备20种RHO-1的变异型酶质粒，其中RHO-1中保守的碱性氨基酸精氨酸和赖氨酸被置换成谷氨酸，将它们在大肠埃希菌中表达并纯化后，用光谱扫描方法在以NADPH-细胞色素P-450还原酶提供电子的模拟体内反应体系下测定变异型酶和野生型酶的活性，从而观察变异型酶的活性是否发生改变。结果变异型酶R35E、K39E、R44E、R136E、K148E、K149E、K153E、R185E和K196E对血红素的降解速度低于野生型酶。结论R35等9个精氨酸残基和赖氨酸残基在参与RHO-1催化血红素降解的反应中对该酶的催化功能有着重要影响。     

血红素加氧酶-1在肾脏功能及血压调节中的作用

Tenhunen于1968年首次提出血红素可被血红素加氧酶(HO)所降解。HO是一种最广泛存在的抗氧化防御酶,是热休克蛋白家族中的成员,主要分布于肺脏、肾脏、脾脏、肝脏、骨髓和网状内皮系统,是血红素代谢的限速酶,能催化血红素生成胆绿素、铁离子和一氧化碳(CO)[1]。HO-1作为其同工酶,     

氯化血红素诱导大鼠肝脏血红素加氧酶1表达对急性乙醇性肝损害的保护作用

目的观察氯化血红素（heroin）对大鼠肝脏血红素加氧酶-1（HO-1）的诱导表达作用，并探讨HO-1对大鼠急性乙醇性肝损害的防治作用。方法SD大鼠28只随机分为三组：模型组（10只），予白酒连续灌胃10d制造急性乙醇性肝损害模型；hemin处理组（10只），在hemin腹腔注射基础上予白酒灌胃；正常对照组（8只），生理盐水灌胃。第10d处死大鼠后检测血清ALT、AST、SOD、MDA水平，光镜观察肝组织细胞形态学改变，采用逆转录聚合酶链反应（RT—PCR）检测肝组织HO-1mRNA表达以及免疫组织化学方法观察HO-1的表达。结果hemin处理组与正常对照组大鼠血清ALT、AST、MDA水平明显低于模型组，SOD水平明显高于模型组。模型组肝细胞肿胀、炎症细胞浸润等形态学改变比hemin处理组与正常对照组明显。hemin处理组HO-1表达明显高于模型组与正常对照组。结论hemin能诱导大鼠肝组织HO-1表达增加，提高HO-1表达对大鼠急性乙醇性肝损伤有保护作用。     

糖尿病足溃疡皮肤血红素加氧酶1表达的研究

目的 探讨血红素加氧酶1(HO-1)在糖尿病足溃疡皮肤中的表达.方法 RT-PCR检测非糖尿病的足溃疡(NDFU)组、糖尿病足溃疡(DFU)组、正常对照(NC)组皮肤HO-1mRNA的表达;免疫组化检测各组HO-1蛋白表达.结果 NDFU组、DFU组、NC组HO-1mRNA表达量分别为:1.880±0.033、1.797±0.024、1.399±0.039,三组间差异有统计学意义;NDFU组和DFU组比较,差异有统计学意义(P均<0.01).HO-1蛋白在NC组表达于表皮;在NDFU组和DFU组表皮和真皮炎症部位均有HO-1阳性细胞,且前者阳性细胞数量多于后者.结论 糖尿病足溃疡较非糖尿病的足溃疡皮肤组织HO-1表达降低.     

辛伐他汀对一氧化氮缺乏性大鼠心肌肥大的抑制作用及机制探讨

目的:观察辛伐他汀对一氧化氮(NO)缺乏性高血压大鼠心肌肥大的作用并探讨其机制。方法:40只大鼠随机分为对照组、模型组、小剂量和大剂量辛伐他汀组。用一氧化氮合酶抑制剂制备心肌肥大模型。6周后测定大鼠心肌肥大指标和心肌血红素氧合酶(HO)活性。结果:模型组动物心肌明显肥大,辛伐他汀治疗组动物较模型组心肌肥大明显减轻,左心室重量指数(LVMI)、心肌BNP含量和羟脯氨酸含量均显著降低(均P<0.01),心肌HO活性明显升高(P<0.01),心肌HO活性与LVMI、心肌羟脯氨酸含量和心肌BNP含量呈明显负相关。结论:辛伐他汀可抑制NO缺乏性大鼠心肌肥大并诱导心肌HO活性升高,HO1CO通路可能是他汀类药物非降脂作用的重要机制之一。     

Heme oxygenase-1 system and gastrointestinal tumors

Heme oxygenase-1(HO-1) system catabolizes heme into three products:carbon monoxide,biliverdin/bilirubin and free iron.It is involved in many physiological and pathophysiological processes.A great deal of data has demonstrated the roles of HO-1 in the formation,growth and metastasis of tumors.The interest in this system by investigators involved in gastrointestinal tumors is fairly recent,and few papers on HO-1 have touched upon this subject.This review focuses on the current understanding of the physiologic...     

Heme oxygenase-1 system and gastrointestinal inflammation: a short review

Heme oxygenase-1(HO-1) system catalyzes heme to biologically active products:carbon monoxide,biliverdin/bilirubin and free iron.It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes.A growing body of evidence indicates that HO-1 activation may play an important protective role in acute and chronic inflammation of gastrointestinal tract.This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible rol...     

Relationships between NOS2 and HO-1 in liver of rats with chronic bile duct ligation.

An increased expression and activity of the heme oxygenase-1 (HO-1) in the liver has been observed in models of hepatic damage. Nitric oxide (NO) seems to be involved in HO-1 regulation. The aim of this work is to assess HO-1 induction and heme oxygenase (HO) activity in rats with bile duct ligation (BDL). We have assessed the effect of chronic inhibition of the NO synthesis by N(G)-nitro-l-arginine methyl ester (l-NAME) on HO-1 induction and HO activity. In the BDL animals, compared with sham-operated ones, we found an increased plasma nitrite and bilirubin concentration, and a marked liver expression of inducible nitric oxide synthase and HO-1, assessed by both Western blot and immunohistochemistry. Chronic l-NAME treatment prevented plasma nitrite increase in animals subjected to BDL. BDL animals treated with l-NAME, compared with untreated BDL rats, showed an important decrease in HO-1 expression and in HO activity (assessed as a decreased plasma bilirubin and bilirubin excretion). In conclusion, our experiments show parallel changes in expression and activity of HO-1 and NOS2 activity in the BDL model of liver damage and suggest that increased NO production is involved in HO-1 overexpression.     

Heme oxygenase-1 alleviates ischemia／reperfusion injury in aged liver

AIM: To investigate if ischemia/reperfusion (I/R) injury in aged liver could be alleviated by heme oxygenase-1 (HO-1). METHODS: Three groups of SD rats (16 mo old) were studied. Group 1: control donors received physiological saline 24 h before their livers were harvested; group 2: donors were pretreated with hemih 24 h before their livers were harvested; and group 3: donors received hemin 24 h before their livers were harvested and zinc protoporphyrin (ZnPP, HO-1 inhibitor) was given to recipients at reperfusion. The harvested livers were stored in University of Wisconsin solution (4℃) for 6 h, and then transplanted to syngeneic rats. Serum glutamic oxaloacetic transaminase (SGOT), apoptotic cells, and apoptotic gene were measured 3, 6, 12, 24, 48 h after reperfusion. We measured the apoptotic index by TUNEL, determined the expression of antiapoptotic Bcl-2 and proapoptotic (caspase-3) gene products by Western blot.. RESULTS: After 3, 6, 12, 24, and 48 h of reperfusion, the SGOT levels (584.4±85.8 u/L, 999.2±125.2 u/L, 423.4±161.3 u/L, 257.8±95.8 u/L, and 122.4±26.4 u/L) in hemin group were significantly (all P<0.05) lower than those in saline group (1082.2±101.2 u/L, 1775.2±328.3 u/L, 840.4±137.8 u/L, 448.6±74.3 u/L, and 306.2±49.3 u/L). Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL+) liver cells 3, 6,12, 24, and 48 h after reperfusion (5.16±0.73, 10.2±0.67, 9.28±0.78, 7.14±1.12, and 4.78±0.65) (P<0.05) could be detected in hemin liver grafts, as compared to controls (7.82±1.05, 15.94±1.82, 11.67±1.59, 8.28±1.09, and 6.36±0.67). We detected the increased levels of Bcl-2 (1.5-fold) expression and compared with saline controls. These differences were most pronounced at 12 h after transplantation. In contrast, an active form of proapoptotic caspase-3 (p20) protein was found to be 2.9-fold lower at 24 h in hemin-pretreated group, as compared to saline liver transplant controls. CONCLUSION: HO-1 overexpression can provide potent protection against cold I/R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism.     

血红素加氧酶-1基因转染对内毒素诱导的ECV304细胞氧化损伤的影响

目的 探讨血红素加氧酶-1( HO-1)基因转染对脂多糖诱导的ECV304细胞氧化损伤的影响.方法 利用逆转录病毒介导的基因转染技术将HO-1基因转染人人脐静脉内皮细胞(ECV304),应用RT-PCR和Western印迹技术检测转染细胞HO-1 mRNA和蛋白表达水平.未转染和转染HO-1基因的ECV304细胞分别培养于含或不含脂多糖(5 mg/L)的DMEM培养基24h后,检测细胞脂质过氧化产物丙二醛(MDA)含量和乳酸脱氢酶(LDH)释放率.结果 HO-1基因和蛋白在转染的ECV304细胞的表达量显著升高.与ECV304细胞相比,转染HO-1基因的ECV304细胞MDA含量和LDH释放率均下降(P＜0.05);应用HO-1抑制剂锌原卟啉共孵育后,转染细胞的MDA含量和LDH释放率增高.结论 HO-1的基因转染可增强ECV304细胞对抗脂多糖氧化损伤的能力.     

慢传输型便秘大鼠结肠诱导型一氧化氮合酶和血红素氧合酶2的变化

目的 探讨慢传输型便秘(STC)大鼠结肠内诱导型一氧化氮合酶(iNOS)和血红素氧合酶2(HO-2)的变化.方法 健康Wistar大鼠32只,随机分为STC组和对照组,每组16只.采用复方苯乙哌啶灌胃法制备STC大鼠模型,饲养100 d后,采用活性炭灌胃法测定肠道传输速度确定模型建立.用免疫组织化学方法分别检测iNOS和HO-2在大鼠结肠的表达情况.结果 STC组大鼠日均粪便粒数、日均粪便干重、日均粪便质量均比对照组明显减少;检测大鼠肠道传输速度,STC组较对照组明显减慢,首粒黑便排出时间较对照组显著延长.iNOS和HO-2在STC大鼠结肠的表达明显强于对照组.结论 iNOS和HO-2在STC大鼠结肠的表达异常,表明iNOS和HO-2在慢传输型便秘发病机制中可能起着重要的作用.     

Heme oxygenase-1 induction by hemin protects liver cells from ischemia/reperfusion injury in cirrhotic rats

AIM： To investigate the potential protective effect of HO-1 on cirrhotic liver cells in rats.
METHODS： Male Wistar rats included in the current study were randomly divided into 5 groups as follows： normal （N） group; liver cirrhotic （LC） group; sham （S） group; I/R group and I/R ＋ hemin group. The model for inducing liver cirrhosis in rats was established according to a previously published protocol. Following this the segmental hepatic ischemia reperfusion operation was carried out. The rats were treated with 30 l~mol/kg hemin （HO-1 inducer, ferric portoporphyrin IX chloride） i.p. or 0.9% NaCI （control） 24 h and 12 h before hepatic ischemia for 30 min or sham laparotomy. Blood was collected for serum enzymatic measurement 6 and 12 h after reperfusion or sham laparotomy. HO-1, NF-κB and caspase-3 expressions were assessed by immunohistochemical analysis.
RESULTS： The expressions of proteins are inversely correlated to the gray values. HO-1 expression in the I/R ＋ hemin group was increased significantly than I/R group at 6 h and 12 h after hepatic I/R （6 h： 112.0± 8.3 vs 125.1± 5.7, P 〈 0.01; 12 h： 120.8± 11.0 vs 132.4 ± 6.2, P 〈 0.01）. Hemin improved serum manganese superoxide dismutase （MnSOD） （6 h： 131.3 ± 17.6 vs 107.0 ± 13.9, P 〈 0.01; 12 h： 141.4 ：E 12.5 vs 118.3± 10.2, P 〈 0.01）, lessened liver cell injury, decreased caspase-3（6 h： 166.7 ± 8.1 vs 145.5 ± 14.6, P 〈 0.01; 12 h： 172.8± 3.8 vs 148.0 ±6.5, P 〈 0.01） and NF-κB expression （6 h： 150.2 ± 8.6 vs 139.7 ±6.0, P 〈 0.01; 12 h： 151.1 ± 5.9 vs 148.1± 5.3, P 〉 0.05） and serum alanine aminotransferase （ALT） （6 h： 413.3± 104.1 vs 626.8 ±208.2, P 〈 0.01; 12 h： 322.2 ± 98.8 vs 425.8 ± 115.4, P 〈 0.05）, aspartate aminotransferase （AST） （6 h： 665.2 ± 70.1 vs 864.3± 70.4, P 〈 0.01; 12 h： 531.1 ± 98.6 vs 664.4± 115.6, P 〈 0.01）, malondialdehyde （MDA） levels （6 h： 11.1 ± 2.17 vs 13.5 ±2.01, P 〈 0.01; 12 h： 9.36