血红素加氧酶1与经皮腔内冠状动脉成形术后再狭窄

血红素加氧酶1是组成微粒体酶系统的重要组分之一,它能催化降解血红素生成胆红素、游离铁离子和一氧化碳。血红素加氧酶1以其强抗氧化、抗炎、抑制血管平滑肌细胞增殖、抑制血小板聚集、调节血管张力及细胞内信号传递等作用,在经皮腔内冠状动脉成形术后再狭窄的防治中发挥重要的作用。     

血红素氧合酶与血压

血红素氧台酶(Heme oxygenase,HO)是血红素代谢过程中的限速酶,可降解血红素生成一氧化碳(CO),胆绿素和铁.HO-1产生的血管保护作用大部分归因于它的代谢终产物所具有的抗炎、抗氧化、抗凋亡、抗血栓形成作用.此外,CO和胆汁酸还可通过影响血管平滑肌细胞、内皮细胞、内皮祖细胞和白细胞等的增殖、迁移、粘附,维...     

血红素加氧酶-1在肝脏缺血再灌注损伤研究中新进展

肝脏缺血再灌注损伤(hepatic ischemia reperfusion injury,HIRI)的分子机制迄今尚未完全清楚。血红素加氧酶-1(heme oxygenase-1,HO-1)是体内血红素降解的起始酶和限速酶,在体内分解血红素生成一氧化碳(CO)、胆绿素和自由铁。HO-1系统具有抗炎、抗氧化、抗凋亡和促进细胞存活、循环稳定和免疫调节的作用,在HIRI中发挥着至关重要的作用。通过药物或基因工程的方法诱导产生HO-1,能减轻HIRI,目前这一方向已经成为该领域的研究热点。     

HO-1在不同病因肝硬化中的研究

肝硬化是多种肝病的终末期阶段,发病机制复杂,炎症及氧化应激在其中发挥重要作用.血红素加氧酶-1(heme oxygenase-1,HO-1)是人体内重要的氧化应激反应蛋白,与其催化血红素的代谢产物(铁、胆红素、一氧化碳)可通过抗炎、抗氧化及调控细胞凋亡等作用共同抑制肝硬化进展.本文对HO-1在不同病因肝硬化中的研究作一...     

血红素氧合酶与肝脏疾病

血红素氧合酶-一氧化碳(HO-CO)系统可在应激状态下激活,有抗氧自由基、抗炎性介质损伤,舒张血管平滑肌等作用,在人体各系统中发挥重要作用.此文就血红素氧合酶在肝病中的研究进行综述.     

内源性一氧化碳对血管紧张素Ⅱ诱导的大鼠血管平滑肌细胞增殖的抑制作用

目的　研究内源性一氧化碳 (CO)对血管紧张素 (Ang )诱导的大鼠血管平滑肌细胞 (VSMC)增殖的影响。方法　体外培养 Wistar大鼠主动脉 VSMC,用 Ang 诱导其增殖 ,分别用血红素氧合酶 1(HO- 1)的诱导剂和阻断剂 ,以诱导和阻断 HO- 1。通过酶联免疫法及同位素技术分别检测培养上清液中碳氧血红蛋白 (COHb)含量及VSMC3H-胸腺嘧啶核苷 (3H - Td R)掺入量。结果　氯血红素 (Hm )显著增高培养上清液中 COHb,对由 Ang 诱导的 VSMC3H - Td R掺入量的增高有显著抑制作用。结论　内源性 CO对 Ang 刺激的 VSMC的增殖有显著抑制作用。提示 HO- CO系统在血管成形术后再狭窄的发生和发展中有一定作用     

血红素氧化酶的心血管系统作用研究

血红素氧化酶的功能是进行血红素代谢,生成一氧化碳、胆红素和铁.一氧化碳增加细胞内环磷鸟苷,调节血管平滑肌张力,产生扩张血管的效应;同时生成的血红素则有抗氧化的作用.本文就血红素氧化酶在心血管系统中的作用机制作一综述.     

血红素加氧酶系统及调控药物与神经系统疾病

在衰老、脑血管疾病和神经变性疾病等生理和病理过程中,氧化损伤发挥着重要作用,机体为了生存必须形成一整套防御机制以保护其免受过氧化损伤。血红素加氧酶是对于细胞自身功能稳定起重要作用的防御酶,血红素加氧酶-1的抗氧化功能部分与其阻止游离血红素参与氧化反应有关,而其代谢产物即CO、胆红素和转铁蛋白均有抗氧化功能,是血红素加氧酶发挥抗炎、抗氧化、抗凋亡和抗增生功能的主要效应分子。血红素加氧酶系统不仅具有重要的生理功能,还参与神经系统疾病的病理生理过程,有效调控其表达有可能成为预防和治疗相关疾病的新策略。现综述血红素加氧酶同工酶的功能及其在衰老、脑血管疾病和神经变性疾病等神经系统疾病中的作用及调控血红素加氧酶系统的药物。     

钾通道与肺动脉平滑肌细胞凋亡

钾通道与肺动脉平滑肌细胞的生长、增殖和凋亡密切相关.在肺动脉高压的发生、发展中起着重要作用.肺动脉平滑肌细胞膜钾通道活性降低或表达下降不仅导致细胞浆游离Ca2+浓度升高,肺动脉平滑肌细胞收缩、增殖和肺血管重构,而且也与肺动脉平滑肌细胞凋亡减少有关.凋亡性容积减少是细胞凋亡的必要前提和早期标志.钾通道参与凋亡性容积减少调节、细胞色素C释放、Caspase激活和DNA降解等凋亡事件以及抗凋亡蛋白Bcl-2、survivin的调节.因此.钾通道有望成为诱导肺动脉平滑肌细胞凋亡药物的靶点,为未来攻克肺动脉高压带来新希望.     

哮喘患者呼出气中一氧化碳增加

一氧化碳(CO)像一氧化氮(NO)一样,具有松弛平滑肌,抑制血小板聚集和作为脑内神经信息递质等生物活性。其来源是通过主要分布于肝脾组织中的由血红素诱导的血红素加氧酶_1和广泛分布不能由血红素诱导的血红素加氧酶_2组成的血红素加氧酶系统,调     

Modulatory effects of carbon monoxide on baroreflex activation in nucleus tractus solitarii of rats

Recent studies suggest that carbon monoxide (CO), which is produced in significant quantities in many brain regions, may function as a neurotransmitter. Heme oxygenase catalyzes the metabolism of heme to CO and biliverdin; however, the physiological role of CO in central cardiovascular regulation was not well understood. In the present study, we evaluated the baroreflex response of CO in the nucleus tractus solitarii (NTS) of rats. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure and heart rate were monitored intra-arterially. Unilateral microinjection (60 nL) of hematin, a heme molecule cleaved by heme oxygenase to yield CO, into the NTS produced prominent dose-related depressor and bradycardic effects. Baroreflex responses were elicited by increasing doses of phenylephrine (10 to 30 microg/kg IV) before and after intra-NTS administration of zinc deuteroporphyrin 2,4-bis-glycol (ZnDPBG) (1 nmol), an inhibitor of heme oxygenase activity, or vehicle alone. The reflex bradycardia elicited by phenylephrine was significantly inhibited by pretreatment with ZnDPBG. Furthermore, the inhibitory effect of ZnDPBG on baroreflex activation was dose dependent. These results suggest CO formed by brain heme oxygenase plays a significant role in central cardiovascular regulation and that inhibition of heme oxygenase attenuated baroreflex activation.     

血红素加氧酶系统及调控药物与神经系统疾病

血红素加氧酶(HO)是体内氧化降解血红素的限速酶,催化血红素生成一氧化碳、胆绿素及铁离子。HO不仅调节细胞内血红素和血红蛋白的水平,而且血红素的3种降解产物均具有生物活性,统称为血红素加氧酶系统(HO/CO系统)。HO/CO系统在衰老、脑血管疾病、神经变性疾病等生理和病理过程中发挥着重要作用,有效地调控其表达有可能成为预防和治疗相关疾病的新策略。     

Interaction of carbon monoxide and adenosine in the nucleus tractus solitarii of rats

Carbon monoxide has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to carbon monoxide and biliverdin. Previously, we have shown the involvement of carbon monoxide in central cardiovascular regulation, baroreflex modulation, and glutamatergic neurotransmission in the nucleus tractus solitarii of rats. We also showed that adenosine increased the release of glutamate in the nucleus tractus solitarii. In this study, we investigated the possible interactions of carbon monoxide and adenosine in the nucleus tractus solitarii. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of increasing doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by heme oxygenase to yield carbon monoxide, produced a significant decrease in blood pressure and heart rate in a dose-dependent manner. In addition, similar cardiovascular effects were observed after injection of adenosine (2.3 nmol). These cardiovascular effects of hemin were attenuated by prior administration of the adenosine receptor antagonist 1,3-dipropyl-8-sulfophenylxanthine. Similarly, pretreatment of the heme oxygenase inhibitor zinc protoporphyrin IX or zinc deuteroporphyrin 2,4-bis glycol also attenuated the depressor and bradycardic effects of adenosine. These results indicate that the interaction between carbon monoxide and adenosine may contribute to the activation of heme oxygenase in central cardiovascular regulation.     

血红素氧合酶/一氧化碳系统在心肌缺血再灌注损伤中的保护机制

血红素氧合酶是血红素降解的限速酶,可将血红素分解为等摩尔的胆绿素、铁和一氧化碳。血红素氧合酶/一氧化碳系统在心肌缺血再灌注中通过血管舒张、抗氧化、抗炎、抗凋亡和抗心律失常作用发挥其保护心肌和心功能的作用。并且其与一氧化氮合酶/一氧化氮系统具有相互调节作用。     

Carbon monoxide and hypertension

The enzymatic action of heme oxygenase yields carbon monoxide, biliverdin and iron. Carbon monoxide is implicated in many physiological processes, including the regulation of vascular tissue contractility and apoptosis. By stimulating the soluble guanylyl cyclase (sGC)/cGMP pathway and activating K channels in vascular smooth muscle cells (SMCs), carbon monoxide relaxes vascular tissues under physiological conditions. Altered metabolism and functions of carbon monoxide have been linked to the pathogenesis and maintenance of hypertension. The expression and activity of heme oxygenase-1, sGC and cGMP in vascular SMCs are associated with different stages of development of hypertension in spontaneously hypertensive rats (SHRs). The importance of altered heme oxygenase-2 expression in vascular tissues in hypertension remains unclear. Increased vascular contractility, unbalanced cellular apoptosis and proliferation in the vascular wall, increased oxidative stress, and the altered interaction of carbon monoxide and nitric oxide are among the consequences of heme oxygenase/carbon monoxide system dysfunction in hypertension. Acute application of pharmacological inducers to upregulate the expression of heme oxygenase-1 or the use of gene delivery method to overexpress heme oxygenase-1 decreases blood pressure in young SHRs and other animal models of hypertension. These blood pressure-decreasing effects are annulled by metalloporphyrins. In adult SHRs, the heme oxygenase/carbon monoxide system appears to be normalized as a compensatory reaction. To date, acute manipulation of the expression of heme oxygenase-1 has not been successful in decreasing blood pressure in adult SHRs. In conclusion, abnormality of the heme oxygenase/carbon monoxide system has a critical role in the pathogenesis of hypertension, and novel therapeutic approaches should be pursued to achieve selective improvement in the function of this system in hypertension.     

血红素氧合酶-1与冠状动脉粥样硬化斑块的稳定性

随着对冠脉综合征研究的深入,我们发现冠脉病变的严重程度主要是由斑块的稳定性决定的。血红素氧合酶是血红素降解的起始酶和限速酶,能代谢血红素形成一氧化碳、游离铁和胆红素。近来研究表明血红素氧合酶-1参与了动脉粥样硬化的发生、发展,与斑块稳定性有着密切的关系。     

Upregulation of heme oxygenase 1 by hemin impairs endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Heme oxygenase converts heme to carbon monoxide, biliverdin (subsequently converted to bilirubin), and free iron. Pharmacological induction of heme oxygenase 1 has an antihypertensive effect in the spontaneously hypertensive rat. The present study investigated whether upregulation of heme oxygenase 1 by hemin reduces endothelial dysfunction in this animal. Thirty-six-week-old rats were divided into a hemin treatment (50 mg/kg, IP injection, once) and a control group. Aortas were isolated for the measurement of isometric tension, production of reactive oxygen species, and heme oxygenase activity, as well as gene and protein expressions. Hemin treatment augmented the expression and activity of heme oxygenase 1. This in vivo induction of heme oxygenase 1, but not in vitro incubation with the heme oxygenase products carbon monoxide or bilirubin, led to an improvement of endothelial function in that acetylcholine-induced relaxations were potentiated and acetylcholine- and calcium ionophore-induced contractions were attenuated. Free radical production was suppressed by hemin treatment, judging from the results of 2',7'-dichlorodihydrofluoresein diacetate staining, dihydroethidium staining, and lucigenin chemiluminescence, which was explained by the decreased expressions of NADPH oxidase 2 and cyclooxygenase 1. The production of prostacyclin was decreased by heme oxygenase 1 induction, which was explained by a lower expression of cyclooxygenase 1. Contractions to vasoconstrictor concentrations of prostacyclin and its mimetic iloprost were attenuated, suggesting that the responsiveness of thromboxane-prostanoid receptors to prostacyclin was decreased in hemin-treated rats. The suppressed production of free radicals and prostacyclin and the decrease of thromboxane-prostanoid receptors sensitivity concur to explain the impairment of endothelium-dependent contractions caused by heme oxygenase 1 induction by hemin.     

血红素加氧酶/一氧化碳通路与高血压

内源性一氧化碳是一种气体信使分子 ,是血红素的降解产物。血红素加氧酶是血红素降解过程的限速酶。由于血红素加氧酶 /一氧化碳通路对心血管系统的多种调节作用 ,而备受关注。本文就一氧化碳的来源、作用机制及其对高血压的作用作一综述。     

血红素氧合酶-1/一氧化碳系统对胰岛素样生长因子-Ⅰ诱导的兔血管平滑肌细胞增殖的抑制作用

目的研究血红素氧合酶-1／一氧化碳（HO-1／CO）系统对胰岛素样生长因子-I（IGF-I）诱导的血管平滑肌细胞（VSMCs）增殖的影响及分子机制。方法体外培养兔主动脉VSMCs,用IGF-I诱导其增殖,用氯化血红素和锌原卟啉-9,分别诱导和阻断HO-1的表达,从而促进和抑制CO生成,通过RT．PCR及Western blot检测HO-1mRNA和蛋白的表达,采用酶联免疫法测定培养上清液中碳氧血红蛋白含量,应用同位素^3H-TdR掺入试验检测VSMCs增殖,采用流式细胞技术检测细胞增殖周期。结果氯化血红素显著诱导VSMCs HO-1 mRNA及蛋白的表达,显著增加VSMCs培养上清液中CO的生成量,呈剂量依赖趋势;梯度浓度的氯化血红素对IGF-I增高的VSMCs ^3H-TdR掺入量抑制率分别为29．6％、45．0％和54．1％,显著抑制细胞周期进程,导致G0／G1细胞显著增多,S期和G2／M期细胞显著减少（P均〈0．01）,与加入的氯化血红素及上清液中碳氧血红蛋白含量呈剂量依赖趋势;锌原卟啉-9则导致相反的结果。结论内源性CO通过抑制VSMCs的DNA合成及细胞周期进程直接参与VSMCs的增殖调节;HO-1表达上调是细胞对抗氧化应激和损伤的保护性反应;HO-1 mRNA及蛋白表达增加是内源性CO抑制VSMCs增殖的基础。