一氧化氮与吗啡镇痛及其镇痛耐受关系的研究进展

近年来,针对吗啡镇痛耐受已经开展了许多研究,通常认为其发生机制非常复杂,涉及许多生物因子和神经传导通路,并且其中的许多因素和环节尚未被完全阐明.一氧化氮(nitric oxide,NO)是中枢神经系统和周围神经系统细胞间和/或细胞内的一种递质,研究发现它在吗啡镇痛作用及其镇痛耐受中发挥着重要调制作用.对此方面的研究进展进行综述,旨在为临床上解决吗啡镇痛耐受这一难题提供有益的启示.     

一氧化氮对女性下尿路作用研究进展

一氧化氮(nitric oxide,NO)作为一种神经递质和信号传导分子,通过与其他神经递质及激素的相互作用,调节膀胱和尿道舒张,在女性下尿路发挥重要生理功能。NO及一氧化氮合酶(nitric oxide syn-thase,NOS)的改变和疾病的发生发展密切相关。     

一氧化氮及其合酶在痉挛桡动脉中的作用

冠脉外科中采用动脉血管移植越来越多，桡动脉因长度足够、口径适当、取材容易而广受重视。但是桡动脉痉挛问题尚未彻底解决，其机制也未阐明。我们比较桡动脉和乳内动脉的一氧化氮(nitric oxide，NO)产量和一氧化氮合酶(nitric oxide synthase，NOS)活性，探讨桡动脉痉挛的原因。     

iNOS/NO对结直肠肿瘤发生发展的影响

一氧化氮（nitric oxide,NO）具有广泛的生物学活性。近年来发现一氧化氮（NO）、一氧化氮合成酶（nitric oxide synthase-2,NOS-2）与结直肠肿瘤的发生、发展密切相关,它与环氧化酶（cy-cloxygenase-2,COX-2）之间存在复杂的调控机制。对NO清除剂、NOS抑制剂和释放NO的非甾体抗炎药的研究为结直肠肿瘤的防治提供了一个思路。     

一氧化氮对女性下尿路作用研究进展

一氧化氮（nitric oxide,NO）作为一种神经递质和信号传导分子，通过与其他神经递质及激素的相互作用，调节膀胱和尿道舒张，在女性下尿路发挥重要生理功能。NO及一氧化氮合酶（nitric oxide synthase,NOS）的改变和疾病的发生发展密切相关。     

一氧化氮和一氧化氮合成酶在急性肺损伤的作用

急性肺损伤(acute lung injury,ALI)是一种发病率和死亡率都很高的常见临床疾病. 目前,对ALI病理生理学基础和临床研究方面的了解越来越多,但并没有提出新的治疗策略能够明显改善ALI的治疗.在ALI的动物模型和患者中,一氧化氮合成酶(nitric oxide synthases,NOS)表达及活性增强和一氧化氮(NO)的增多在ALI的病理生理过程中有重要作用;但临床抑制NO生成以及选择性抑制NOS并没有对ALI的治疗有明显效果.目前提出了不同细胞源性NO的概念,这种NO的细胞源性差异可能对ALI的治疗有潜在的意义.现综述NO和NOS在ALI中的作用.     

PVAT介导NO/NOS在脓毒血症患者血管舒缩活动中的作用研究进展

脓毒血症是一种严重的致命性疾病,多种机制参与其发生及演进过程。血管周围脂肪组织（perivascular adipose tissue, PVAT）作为心血管疾病中的重要参与者,与血管关系密切,同时可分泌多种活性物质参与血管舒缩活动的改变。一氧化氮（nitric oxide, NO）及一氧化氮合酶（nitric oxide synthase, NOS）是重要的舒血管物质。本综述通过回顾既往文献资料,对PVAT介导NO/NOS在脓毒症中血管张力调节的机制做一探讨,以期有助于后续的研究实践及临床工作。     

一氧化氮在软骨病变中的作用

一氧化氮(nitric oxide,NO)是一种脂溶性小分子,参与炎症反应、免疫调节及血管舒张等多种生理病理过程.自1991年Stadler[1]首先报道兔关节软骨细胞在IL-1和脂多糖作用下能产生一氧化氮以来,研究者和临床医生开始关注NO与关节软骨之间的关系.NO参与关节软骨生理和病理过程的各个环节的调节.本文将对NO在软骨病变中的作用做一综述.     

一氧化氮与疼痛的研究进展

一氧化氮(NO)作为一种神经递质和信息传递分子,在外周和中枢不同水平的痛觉调制中发挥重要作用。许多研究表明在体内抑制NO的生成可以达到镇痛作用。目前一氧化氮合酶(NOS)抑制剂作为镇痛药物在临床应用中显示出较好的前景。     

一氧化氮与疼痛的研究进展

一氧化氮(NO)作为一种神经递质和信息传递分子，在外周和中枢不同水平的痛觉调制中发挥重要作用。许多研究表明在体内抑制NO的生成可以达到镇痛作用。目前一氧化氮合酶(NOS)抑制剂作为镇痛药物在临床应用中显示出较好的前景。     

大鼠肝缺血／再灌注后肝组织一氧化氮和不同亚型一氧化氮合酶的变化

目的探讨一氧化氮（NO）和一氧化氮合成酶（NOS）在肝缺血／再灌注（I／R）过程中的变化和作用。方法健康雄性SD大鼠24只，随机分为3组（每组8只）：①正常对照组，术中只分离肝周围韧带，不做肝门阻断及再灌注。②I/R组，进行45min的部分肝门阻断及60min的再灌注。③L-精氨酸（L—Arg）组，缺血前20min经阴茎背静脉注射L—Arg（300mg／kg），余同②组。实验结束后，取下腔静脉血2ml，并迅速切取缺血肝组织。检测血清丙氨酸转氨酶（ALT）、门冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）；测定肝组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、黄嘌呤氧化酶（XOD）、一氧化氮（NO）和一氧化氯合成酶（NOS）等指标；观察光镜和电镜下肝组织学变化。结果与正常对照组相比，I／R组iNOS升高，NO降低；L-Arg组NO、eNOS均高于I／R组。2、3组比1组大鼠的肝组织病理损害重、肝功能差，L—Arg组病理损害较I／R组明显减轻、肝功能改善。结论NO对大鼠肝I／R损伤具有保护作用．不同亚型NOS的变化参与其中。     

Sedative but not analgesic alpha2 agonist tolerance is blocked by NMDA receptor and nitric oxide synthase inhibitors

BACKGROUND: Studies show that the sedative and analgesic effects of alpha2 adrenergic agonists decrease over time, which is a form of synaptic plasticity referred to as tolerance. Because both the N-methyl-D-aspartate (NMDA) receptor complex and nitric oxide synthase are pivotal for some forms of synaptic plasticity, their role in tolerance to the hypnotic and analgesic effects of alpha2 agonists was investigated. METHODS: After institutional approval, rats were made tolerant to the hypnotic or analgesic action of an alpha2 agonist, dexmedetomidine. The hypnotic response to dexmedetomidine was assessed by the duration of loss of righting reflex, and the analgesic response to dexmedetomidine was assessed by the tail-flick assay. In separate cohorts, either the NMDA receptors or nitric oxide synthase was antagonized by coadministration of MK-801, ketamine, or NO2-arginine, respectively, during induction of tolerance. In a separate series of experiments, after tolerance was induced, the hypnotic and analgesic responses to dexmedetomidine were assessed in the presence of acutely administered MK-801 or NO2-arginine. RESULTS: Induction of tolerance to the hypnotic effect of dexmedetomidine is blocked by coadministration of MK-801, ketamine, and NO2-arginine. However, after tolerance developed, acute administration of MK-801, ketamine, or NO2-arginine did not prevent the expression of tolerance. Coadministration of MK-801 or NO2-arginine neither prevents the development nor reverses the expression of tolerance to the analgesic action of dexmedetomidine. CONCLUSION: The underlying processes responsible for the development of tolerance to the hypnotic and analgesic actions of systemically administered alpha2 agonists were different, with only the sedative tolerance involving the NMDA receptor and nitric oxide synthase system.     

Vaccinia virus-induced inhibition of nitric oxide production

BACKGROUND: The role of nitric oxide (NO) in the host defense against viruses has not been well defined. Several studies have implicated NO as responsible for the destruction of a variety of viruses. However, others have reported that certain viruses can impair the ability of macrophages to produce NO. This study was initiated to determine the ability of macrophages to produce NO in response to vaccinia virus infection. METHODS: RAW 264.7 murine macrophages in minimum essential medium were exposed to virus-containing supernatants for 1 h before stimulation with Escherichia coli lipopolysaccharide (LPS, 0.001 and 1.0 microg/ml). After further 24-h incubations, nitrite concentration, cell viability, and inducible nitric oxide synthase (iNOS) were quantitated. RESULTS: The viral preparation alone did not stimulate nitric oxide synthesis (measured as nitrite) by macrophages. However, macrophages exposed to 0.001 and 1.0 microg/ml LPS produced 7.7 +/- 0.6 and 16.6 +/- 0.8 nmole/1.1 x 10(6) cells/24-h nitrite, respectively. Production of nitrite caused cell death. Macrophages incubated with vaccinia virus prior to exposure to LPS resulted in a dose-dependent decrease in nitrite production. An 80% inhibition of nitrite was noted when macrophages were exposed to vaccinia virus (m.o.i. 10(-4)) plus LPS (1.0 microg/ml) (P < 0.05). Further study showed that this inhibition was not associated with changes in cell viability or substrate availability, but was associated with a marked reduction in iNOS protein. When the virus was inactivated with UV-irradiation, the same incubation caused a 46% inhibition of nitrite production (P < 0.05 vs active virus). However, this effect occurred without altering the quantity of iNOS protein. CONCLUSION: These results indicate that active vaccinia virus inhibits the ability of stimulated macrophages to produce NO by hindering iNOS protein expression. Because live viral particles were not entirely required for this inhibition, it is possible that by products of viral infection, such as soluble viral proteins, may also be responsible for this effect.     

Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide

This review describes the laboratory evidence and microvascularmechanisms responsible for the beneficial effects of statinsin sepsis. During sepsis, changes occur within the microcirculationincluding alterations in arteriolar tone influencing blood pressure,adaptations to endothelial cell integrity causing leakage ofproteins and macromolecules, and adhesion and migration of leucocytesthrough the vascular endothelium. Statins are widely used ascholesterol-lowering agents, but appear to have anti-inflammatoryactions during sepsis. We have discussed the effects of statinson specific pathological processed within the microcirculationand focused on the role of nitric oxide (NO). The main mechanism by which statins appear to be an effectivetreatment for sepsis is increased expression of endothelialnitric oxide synthase (eNOS), in conjunction with down-regulationof inducible nitric oxide synthase. Combined, this results inan increase in physiological concentrations of NO, thus restoringendothelial function. Laboratory studies have therefore suggestedthat enhancement of eNOS activity during sepsis may lead torestoration of microvascular tone, maintenance of microvascularintegrity, and inhibition of cell adhesion molecules. However,other mechanisms independent of lipid-lowering effects, includingantioxidant activity and alterations in the development of vascularatherosclerosis, may also contribute to the beneficial effectsof statins. We have also addressed the influence on the effectsof statins of lipid solubility and pre- and pro-phylactic administration.     

Significance of nitric oxide and its modulation mechanisms by endogenous nitric oxide synthase inhibitors and arginase in the micturition disorders and erectile dysfunction

Abstract:   Evidence indicates that nitric oxide (NO) deficiency contributes to micturition disorders, especially in the afferent pathway and erectile dysfunction (ED). Two possible causes of NO deficiency are substrate ( l -arginine) limitation and increased levels of endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine: ADMA) in plasma and tissues. Elevated tissues of ADMA and N^G-monomethyl-L-arginine (L-NMMA) have been reported to be associated with impaired NO-mediated urethral, trigonal and cavernosal relaxations by pelvic ischemia. Also, plasma ADMA may help to identify underlying cardiovascular disease in men with ED. Decreased l -arginine availability to NO synthase is due to the shunting of l -arginine into other pathways such as arginase. Interaction between NO synthase and arginase has been reported to be involved in NO-mediated urethral and prostatic relaxations. Also, increased arginase activity in cavernosal tissues likely contributes to the ED that accompanies diabetes mellitus and aging. Therefore, arginase inhibition has been reported to enhance the NO-dependent physiological process for erectile function.     

Layer-specific production of nitric oxide during cortical circuit formation in postnatal mouse brain

In the developing cerebral cortex, neuronal nitric oxide synthase (nNOS) is expressed abundantly, but temporarily. During the early postnatal stage, cortical neurons located in the multi-layered structure of the cortical plate start forming well-organized cortical circuits, but little is known about the molecular machinery for layer-specific circuit formation. To address the involvement of nitric oxide (NO), we utilized a new NO indicator (DAR-4M) and developed a protocol for the real-time imaging of NO produced in fresh cortical slices upon N-methyl-D-aspartic acid stimulation. At postnatal day 0 (P0), NO production was restricted to the deep layers (layers V and VI) of the somatosensory cortex where transient synapses are formed. At P10, the production of NO was expanded to layer IV where large numbers of thalamocortical axons form synapses. The pattern of NO production could correspond to active sites for synaptic formation. This study is the first clear demonstration of NO production in the postnatal mouse neocortex. The findings presented may reflect a function of NO in relation to the layer-specific development of neural circuits in the neocortex.     

冠状动脉旁路术围术期肺动脉血浆一氧化氮合成酶活性与一氧化氮浓度的变化

目的 研究冠状动脉旁路术围术期肺动脉血浆一氧化氮合成酶（NOS）活性和一氧化氮（NO）浓度的变化。方法 选择30例冠状动脉旁路手术（CABG）病人,在围术期抽取肺动脉血测定NOS和NO值。结果 肺动脉血浆中NOS和NO水平虽有明显变化（P＜0．05）,但NO浓度与NOS活性的增减并不一致：当NOS活性降低时,NO浓度增高;反之当NOS活性显著增高时,NO浓度降低。结论 在行CABG围术期中,肺动脉血浆中内源性NO分泌无法满足应激时自身保护对其的需要。     

Activity of nitric oxide synthase in mature and immature human spermatozoa

Nitric oxide (NO) is known to be involved in multiple signal transduction pathways of male germ cells, including sperm capacitation. In somatic cells, NO production was found to be part of apoptosis signalling. The aim of our study was to further clarify the role of NO in spermatozoa by investigation of NO synthase activity with regard to sperm maturity and sperm apoptosis signalling. Semen specimens from 19 healthy donors were subjected to density gradient centrifugation to separate the predominantly mature and immature sperm fraction. NO synthase activity was evaluated using diaminofluoresceine‐2‐diacetate by FACS. Apoptosis signalling was monitored by flowcytometric analyses of caspase‐3 (CP3) and integrity of the transmembrane mitochondrial potential (TMP). TUNEL assay was used to detect DNA fragmentations. Maturity of human spermatozoa was associated with increased NO synthase activity and inactivated apoptosis signalling (lower levels of disrupted TMP, active CP3 and DNA fragmentations, P < 0.05). Activation of apoptosis signalling was significantly negatively correlated to NO production, indicating a rather anti‐apoptotic effect of NO. This might underline the recently proposed role of NO in physiological sperm signal transduction, e.g. during capacitation.