Nitric Oxide in Inflammation and Immune Response

This short review deals with the role of a recently found signalling molecule, nitric oxide (NO), in inflammatory and immune responses. NO regulates inflammatory erythema and oedema and has cytotoxic action against micro-organisms. In some instances (such as reperfusion injury) NO has cytoprotective properties. Production of large amounts of NO by activated macrophages accounts for their ability to suppress lymphocyte proliferation. NO synthesis in lymphocytes is questionable but cytokines secreted by activated lymphocytes regulate NO synthesis by macrophages. Constitutive NO synthase is activated in neutrophils in response to inflammatory stimuli and NO has diverse, often biphasic effects on neutrophil functions. Increased concentrations of nitrite and nitrate (metabolites of NO) are present in arthritic joints. NO is synthesized not only by migrated inflammatory cells but also by articular chondrocytes and inflamed synovial membrane. In the inflamed joint, NO regulates the synthesis of several inflammatory mediators and functions of inflammatory cells. In addition, NO seems to mediate some destructive effects of proinflammatory cytokines such as interleukin-1. In conclusion, NO regulates several humoral and cellular responses in inflammation, having both anti-inflammatory and proinflammatory properties depending on the type and phase of the inflammatory reaction.     

一氧化氮供体诱导HL-60细胞凋亡过程中活性氧自由基和抗氧化能力的变化

为了研究外源性一氧化氮（NO）供体硝普钠（SNP）诱导HL-60细胞凋亡过程中活性氧自由基和抗氧化能力的变化，将HL-60细胞与SNP在体外培养，用MTT法观察NO对细胞的抑制作用；用透射电子显微镜和光学显微镜观察细胞结构的变化；用DNA凝胶电泳、细胞DNA含量、Annexin-V／PI法等分析细胞凋亡；用双氢罗丹明123（DHR）标记、流式细胞仪检测细胞内活性氧（ROS），并同时测定细胞内谷胱甘肽（GSH）和3种抗氧化酶的活性。结果表明：SNP能抑制HL-60细胞生长，典型的细胞形态改变、DNA片段化、亚二倍体峰比例增加、DNA末端标记和Annexin-V^＋／PI^-表达增加等证实NO能诱导白血病细胞凋亡，且两者之间有明显的量效和时效关系。在此过程中，细胞内ROS水平增加，细胞内谷胱甘肽和过氧化氢酶（CAT）、谷胱甘肽S转移酶（GST）、谷胱甘肽过氧化物酶（GPX）活性降低。ROS含量和CAT、GST、GPX活性与SNP之间也有明显的量效关系。结论：细胞内活性氧自由基增加和抗氧化能力下降在外源性一氧化氮供体诱导HL-60细胞凋亡中发挥了重要作用。     

脑梗死患者一氧化氮合酶基因多态性及其对一氧化氮的影响

目的观察脑梗死患者内皮型一氧化氮合酶(eNOS)基因多态性及一氧化氮(NO)变化情况。方法采用前瞻性病例对照研究,脑梗死组193例,均为发病2周内经头颅CT或MRI证实存在颈内动脉分布区梗死灶者,对照组103例为正常体检者。对两组eNOS基因4号内含子多态性进行测定,并采用Griess重氮化反应法和酶标法分别检测血清NO含量、NOS活性。结果脑梗死组eNOS基因4号内含子a等位基因(eNOS4a)携带者48例,对照组为12例,携带频率有显著性差异(χ2=8.86,P=0.003);经Logistic回归分析,eNOS4a携带是脑梗死的独立危险因素(P=0.032);脑梗死组NO产物浓度中位数为6.04(3.83～11.49)μmol/L,低于对照组6.89(4.64～12.43)μmol/L(P=0.022)。eNOS4a携带者NO产物浓度中位数为5.07(3.18～7.62)μmol/L,低于非携带者6.86(4.39～11.76)μmol/L(P=0.001)。脑梗死组NOS活性为(2.97±1.47)U/ml,对照组(3.16±1.46)U/ml,无显著性差异(P=0.517)。eNOS4a携带者NOS活性(2.77±1.13)U/ml,与非携带者(3.12±1.54)U/ml无显著性差异(P=0.100)。结论eNOS4a携带可能通过减少NO生成而在脑梗死发生过程中发挥作用。     

精神分裂症患者一氧化氮合酶活性与发病机制相关性

目的通过测定首发精神分裂症患者和正常人的血清一氧化氮合酶(NOS)活性,比较和分析他们之间的差异,探讨NOS活性以及一氧化氮(NO)能神经系统的功能变化与精神分裂症的关系。方法采用比色法分别测定首发未用抗精神病药的精神分裂症患者(研究组)、临床症状缓解的精神分裂症患者(缓解组)和正常对照者的血清NOS活性。结果研究组的血清NOS活性为6.3665±1.2260(n=39),明显高于症状缓解组(4.1204±0.9908,n=27,P<0.01)和正常对照组(3.2660±1.0320,n=27,P<0.01);症状缓解组的NOS活性也明显高于正常对照组(P<0.01)。结论精神分裂症患者血清NOS活性明显增高,L-精氨酸-NO神经通路功能的紊乱可能是精神分裂症的发病机制之一,也可能成为一个新的治疗靶系统。     

Nitric oxide in vascular biology

Summary.  Nitric oxide is a highly versatile heterodiatomic molecule that effects a variety of actions in the vasculture. Originally identified as a principal determination of vascular tone, nitric oxide has since been recognized to exert anti thrombotic, antiproliferative, and anti-inflammatory effects in the vasculture. At higher concentrations and in the setting of other oxidants, nitric oxide can promote vascular pathology. In this review, we summarize the molecular mechanisms of nitric oxides actions in vascular biology and pathology.     

Nitric Oxide in Hypertension and Renal Diseases

Nitric oxide (NO) is intimately involved in the regulation of vascular tone, renal haemodynamics and sodium balance. The physiological actions of NO suggest important vascular and renal protective roles for NO. When produced in large amounts, however, NO may also mediate cytotoxic effects. Increasing evidence suggests that endothelial function, notably the NO pathway, may be compromised in hypertension. It is not known, however, whether changes in endothelial function are primary or secondary to the development of hypertension. In renal diseases evidence for both excessive and deficient activity of NO pathway has been found. Increased glomerular production of NO via inducible NO synthase (NOS) with potential cytotoxic consequences has been demonstrated in experimental acute glomerulonephritis. On the other hand, indirect evidence obtained by means of NOS inhibitors point out to an important renoprotective role for NO in renal diseases. NO may counteract disease progression in renal diseases by preventing glomerular microthrombi, maintaining renal perfusion and medullary oxygenation, and via its anti-inflammatory/antiproliferative effects. However, these beneficial effects of NO may be compromised (endothelial and/or tubular dysfunction) in chronic nephropathies resulting in an accelerated course of renal disease. In future, more specific inhibitors and activators of different NOS isoforms are needed to elucidate the role of NO in various renal diseases in detail, and for treatment strategies aimed at modifying the NO pathway.     

一点红用于经口气管插管患者口腔护理的效果观察

目的评估采用一点红对经口气管插管（oral endotracheal tube,OETT）患者进行口腔护理的应用效果。方法将60例OETT患者按气管插管的时间先后编号随机分成试验组和对照组各30例,试验组采用一点红进行口腔护理,对照组采用复方硼砂液进行口腔护理。观察两组在插管后7d内口腔溃疡发生率、发生时间。结果两组患者口腔护理后口腔溃疡发生率差异有统计学意义（P〈0．005）,试验组口腔溃疡发生率低于对照组;两组患者发生口腔溃疡的时间差异有统计学意义（P〈0．01）,试验组口腔溃疡发生时间明显比对照组晚。结论采用一点红口腔护理明显优于复方硼砂液,对防止和控制OETF患者口腔感染有积极意义。     

Nitric Oxide: Biological Mediator,Modulator and Effector

Nitric oxide (NO) is synthesized from L-arginine by at least three isoforms of NO synthase enzyme (NOS). Once generated NO can interact with a number of molecular targets including haem proteins, enzymes, DNA, thiols, oxygen and superoxide. These reactions determine the profile of NO as a major biological mediator, modulator and effector molecule.     

血清中一氧化氮浓度与精子活动度关系的分析

目的探讨个体血清一氧化氮浓度对精子运动能力的影响。方法用721分光光度计测定血清中一氧化氮浓度,用OLYMPUS显微摄影系统等自动分析精子的运动情况。结果一氧化氮浓度在60~93μmol／L之间时显著促进精子的运动,一氧化氮浓度过高(>93μmol／L)和过低(≤59μmol／L)都会抑制精子的运动。结论精子运动能力与个体血清中一氧化氮浓度有关。     

血清一氧化氮及一氧化氮合酶水平与病毒性肝炎的关系

【目的】探讨血清一氧化氮 (NO)及一氧化氮合酶 (NOS)水平与病毒性肝炎的关系。【方法】作者检测了 5 9例病毒性肝炎患者的血清NO及NOS水平。【结果】各型肝炎患者的NO含量均显著高于正常对照组 (P <0 .0 1) ,NOS含量以肝硬化 (LC)、急性肝炎 (AVH)、重型肝炎 (HG)增高显著 (P <0 .0 1) ,其中以LC组增高最为明显。在急性、慢性、重型肝炎的急性期或活动期时 ,NO含量与谷丙转氨酶 (ALT)及总胆红素 (TBIL)呈正相关。【结论】肝脏发生炎症时 ,NOS被诱导生成增多 ,从而产生大量的NO。NO含量升高与肝功能损害的程度有关。重症肝炎时 ,由于肝细胞大量坏死 ,导致NOS降低 ,NO生成也相应减少。肝硬化患者的血清NO及NOS增高 ,主要与内毒素有关     

血吸虫病人血一氧化氮测定意义探讨

目的 :探讨血吸虫病人血一氧化氮测定的意义。方法 :分别测定 32例慢性血吸虫病人 ,11例晚期血吸虫病人和 30例正常人血一氧化氮 ,并进行统计分析。结果 :晚期血吸虫病人和慢性血吸虫病人血一氧化氮显著高于正常人 (P <0 .0 5 ) ,晚期血吸虫病人的血一氧化氮水平也非常显著地高于慢性血吸虫病人 (P <0 .0 1)。结论 :血一氧化氮水平与血吸虫病关系密切 ,动态观察血一氧化氮水平的变化对掌握血吸虫病情的发展有重要意义     

一氧化氮在维甲酸诱导分化治疗中的作用

一氧化氮(nitric oxide,NO)作为一种效应分子,参与杀灭病原微生物和攻击肿瘤细胞等细胞毒效应。现在越来越多的证据表明,NO也能影响造血细胞的生长、分化和凋亡,与维甲酸诱导分化治疗作用有关。通过研究NO在维甲酸诱导分化过程中的作用,就可以从另一个角度探讨维甲酸作用的分子机理,为逆转维甲酸耐药和减少维甲酸综合征提供新的思路。     

妊娠高血压综合征患者血浆一氧化氮与内皮素-1的变化及其意义

本文应用Ｇｒｉｅｓｓ法及放射免疫法测定６０例妊娠高血压综合征患者、２３例正常晚期妊娠妇女、２２例健康非孕妇女血浆ＮＯ－２／ＮＯ－３和ＥＴ－１水平。结果表明：妊高征患者血浆ＮＯ－２／ＮＯ－３下降，ＥＴ－１上升。两者呈明显负相关。本文结果提示：一氧化氮与妊高征病情呈负相关；ＥＴ－１与妊高征病情呈正相关；ＮＯ和ＥＴ－１在妊高征中呈负相关。ＮＯ／ＥＴ－１比值越小，妊高征病情越重。     

Nitric Oxide in the Central Nervous System

The majority of the data on nitric oxide (NO) in the central nervous system (CNS) relies on histochemical and immunesohistochemical evidence concerning the distribution of the nitric oxide synthase (NOS), its inhibition by specific antagonists and its co-localization with the receptor enzyme guanylate cyclase (GC) in the same functional region. All three isoforms, endothelial (eNOS), neural (nNOS) and macrophage type inducible (iNOS), are of importance to the normal and pathological function of the CNS. In nNOS gene deleted mice eNOS seems to contribute to the maintanace of neuronal function. NO may contribute to synaptic plasticity as a retrograde mediator that is released by postsynaptic NMDA-receptor activation. Microglia contains membrane-bound inducible iNOS that may be important in host defence function. Glia and pericytes surrounding the blood vessels contain GC that is stimulated by NO released from endothelium and nerve endings. Excessive production of highly reactive NO may be responsible for the neurotoxicity mediated by NMDA receptors that contributes to the symptomatology of strokes and neurodegenerative diseases. Moreover, after initial stimulation by cytokines, large amounts of NO produced by iNOS in the microglia (brain-based macrophages) may cause cellular damage.     

Exhaled Nitric Oxide Levels during Acute Asthma Exacerbation

Objectives: Fractional exhaled nitric oxide (FE_NO) has been shown in laboratory settings and trials of patients with stable asthma to correlate with the degree of airway inflammation. The authors hypothesized that the technique of measuring FE_NO would be reproducible in the setting of acute asthma in the emergency department (ED) and that the FE_NO results during ED visits would potentially predict disposition, predict relapse following discharge, and correlate with the National Institutes of Health (NIH) asthma severity scale and peak expiratory flow measurements. Methods: The authors prospectively measured FE_NO in a convenience sample of ED patients with acute exacerbations of asthma, both at the earliest possible opportunity and then one hour later. Each assessment point included triplicate measurements to assess reproducibility. The authors also performed spirometry and classified asthma severity using the NIH asthma severity scale. Discharged patients were contacted in 72 hours to determine whether their asthma had relapsed. Results: The authors discontinued the trial (n= 53) after a planned interim analysis demonstrated reproducibility (coefficient of variation, 15%) substantially worse than our a priori threshold for precision (4%). There was no association between FE_NO response and corresponding changes in spirometry or clinical scores. Areas under the receiver operating characteristic curves for the prediction of hospitalization and relapse were poor (0.579 and 0.713, respectively). Conclusions: FE_NO measurements in ED patients with acute asthma exacerbations were poorly reproducible and did not correlate with standard measures of asthma severity. These results suggest that using existing technology, FE_NO is not a useful marker for assessing severity, response to treatment, or disposition of acute asthmatic patients in the ED.     

一氧化氮与青光眼视功能损害的关系

目的 :探讨一氧化氮 (NO)在青光眼患者视功能损害中的作用及机制 ,为患者视功能的康复提供新的思路。方法 :5 5例青光眼患者根据视功能损害程度和沿盘面积比分为 3个阶段 ,即早期青光眼 16例 ,进展期青光眼 2 1例和晚期青光眼 18例 ,另设正常志愿者 30例 (正常组 ) ,应用化学比色法测定其血浆中NO的含量。结果 :青光眼患者血浆中NO的含量水平较正常组显著减少 (P <0 .0 1) ,早期NO水平降低 ,进展期和晚期降低更显著 ;沿盘面积比与NO水平呈负相关。结论 :青光眼患者血浆中NO的含量减少与青光眼视功能损害程度有关。     

Nitric oxide and its relationship to thrombotic disorders

Summary.  Nitric oxide (NO) is released by the endothelium preventing platelet adhesion to the vessel wall. When released by platelets, NO inhibits further recruitment of platelets to a growing thrombus. Modulation of endogenous NO release may be a mechanism by which the thrombotic response can be regulated as suggested by several clinical diseases associated with impaired bioactive NO. Diseases including atrial fibrillation and coronary atherothrombotic disease have been associated with impaired NO release or decrease in NO bioavailability.