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。     

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。     

一氧化氮--一氧化氮合酶系统与骨折愈合

一氧化氮（nitric oxide,NO）是在一氧化氮合酶（nitric oxide sythase,NOS）作用下氧化产生的一种小分子自由基气体.由于其分子量小,脂溶性及化学性质活泼,因而极易透过生物膜,是细胞间、细胞内的重要信使分子.由于其合成易于调节,作为高级生物体,调节的有效信号在循环、呼吸、消化及内分泌代谢等系统中发挥着重要作用.近几年来的研究发现,NO-NOS系统对骨折愈合起重要作用.本文就NO-NOS系统对骨折愈合的影响作一综述.     

一氧化氮与肿瘤血管形成及转移研究进展

自20世纪80年代后期,人们在对离体的哺乳动物巨噬细胞研究中逐步发现一氧化氮(nitric oxide,NO)这一自由基性质的活性分子.很快在生理学、神经科学和免疫学等领域证明了NO既有第二信使和神经递质的性能,又是杀伤肿瘤细胞的效应分子.其与肿瘤生物学的关系成为最近NO研究的新热点.NO首先在内皮细胞被识别,但已知许多细胞,包括一些肿瘤细胞系和实体瘤组织也产生NO.本文简要综述近年NO在肿瘤血管形成、肿瘤转移过程中的作用及临床应用前景.     

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.     

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目的 探讨一氧化氮（nitric oxide,NO)在胆管癌细胞凋亡中的作用机制。方法 通过细胞培养,采用流式细胞仪等测定体外培养胆管癌细胞QB内NO含量,同时检测不同水平NO细胞内细胞凋亡率。结果 低浓度NO对胆管癌QB细胞凋亡无影响,高浓度的NO明显促进QB细胞的凋亡发生。结论 NO对胆管癌细胞内细胞凋亡具有双重作用。     

损伤性氧化反应在腹主动脉瘤形成中的作用

目的探讨诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）在人腹主动脉瘤（abdominal aortic aneurysm，AAA）组织中的表达情况，了解一氧化氮（nitric oxide，NO）在人AAA形成中的作用。方法22例AAA患者及10例正常人腹主动脉组织标本。采用原位杂交及免疫荧光染色的方法探查iNOS mRNA及蛋白的表达。采用原位杂交联合免疫荧光染色的方法探查阳性细胞的性质。采用免疫荧光染色检测过氧化亚硝酸盐。结果原位杂交和免疫荧光发现iNOS在22例AAA组织中外膜均有表达。联合免疫荧光染色证实阳性细胞分别为：T、B淋巴细胞、巨噬细胞和平滑肌细胞（smooth muscle cell，SMC）。22例AAA均出现硝基酪氨酸的表达，阳性细胞为巨噬细胞和SMC。10例正常腹主动脉组织均没发现有iNOS和硝基酪氨酸的表达。结论iNOS的表达与人AAA组织的退行性变关系密切。iNOS促进过氧化亚硝酸盐的生成，导致组织和细胞的氧化损伤。     

一氧化氮对急性胆道感染大鼠肾功能影响作用研究

目的　探讨一氧化氮（nitric oxide,NO）对实验性急性胆道感染大鼠肾功能的影响作用。方法　Wistar大鼠35只,随机分为急性胆道感染组（AC组）、急性胆道感染加左旋精氨酸组（L组）、左旋硝基精氨酸甲基酯组（N组）、单纯胆道梗阻对照组（O组）和假手术组（SO组）5组,分别测定血浆NO、BUN、Cr值和肾组织一氧化氮合成酶（NOS）活性,并行肝、肾组织病理变化观察。结果　L组NO、NOS高于其余各组（P＜0.05）,BUN、Cr低于AC组和N组（P＜0.05）,而与O组比较差异无显著性意义（P＞0.05）,肾组织病理变化较AC组轻;N组NO、NOS低于其余各组,而BUN、Cr则高于其余各组（P＜0.05）。结论　NO对急性胆道感染72小时大鼠的肾功能有保护作用,其作用机理可能与其舒张肾血管,增加血液灌流量等作用有关。     

一氧化氮及一氧化氮合酶与吗啡耐受关系的新进展

疼痛治疗中长期给予吗啡易导致严重的耐受问题.多年来,针对耐受机制的研究表明NMDA/NO级联反应参与耐受的发生及发展.一氧化氮(nitric oxide,NO)主要是由一氧化氮合酶(nitric oxide synthase,NOS)催化其惟一前体--L-精氨酸生成NO和瓜氨酸.研究者们证实了大鼠鞘内吗啡耐受后脊髓内NOS尤其是nNOS的表达增高,耐受机制主要通过N-甲基-天门冬氨酸(N-methyL-D-aspartate,NMDA)受体的激活以及胞内钙离子浓度的升高来调节NOS的活性而触发NMDA/NO级联反应,继而影响耐受的发展.诸多研究给予吗啡的同时给予NOS抑制剂可以阻止耐受的发生,甚至在耐受形成后应用NOS抑制剂也可以翻转已经建立的耐受.但证实NOS各亚型在耐受中的具体作用仍不明确,需开展相关的研究进一步阐述其间的关系.     

Regulation of nitric oxide synthesis in uraemia

Nitric oxide (NO) is a cell-to-cell mediator involved in theregulation of vascular tone and in the mechanisms of host defence.Since uraemic syndrome is characterized by abnormalities inblood pressure and flow and by impairment of white cell function,we studied the regulation of nitric oxide synthase (NOS) activityby uraemic plasma. We used three different cellular types havingdifferent levels of NOS activity: tEnd. 1 murine endothelialcell line transformed by mT oncogene of polyomavirus had a highNOS activityand expressed endothelial-NOS (eNOS) and inducible-NOS(iNOS) isoforms; human endothelial cells from cord umbilicalvein (HUVEC) had low enzymatic activity and expressed only eNOS;finally, J774 murine macrophage line was characterised by iNOSinduced after treatment with cytokines. We demonstrated thatmost (79%) of end-stage uraemic plasma studied inhibited NOSactivity in tEnd.1 and in cytokine induced -J774, whereas theywere ineffective on HUVEC. Twenty percent of plasma samples(14 of 67) activated NOS activity in tEnd.1 and in J774 cells,but not in HUVEC, suggesting the presence of molecule(s) whichinfluence iNOS. The effect of plasma was not dependent on thetype of haemodialysis treatment. A great number of plasmas frompatients with moderate renal failure also inhibited NOS activityin tEnd.1, suggesting that the accumulation of molecules affectingNOS was caused by the renal failure rather than the haemodialytictreatment. However, the haemodialysis modified the effect of plasmas onNOS activity. Plasma taken after haemodialysis session showeda reduced inhibitory activity in tEnd.1 and in some cases itenhanced NOS activity. Simultaneously, molecules reducing NOSactivity accumulated in the ultrafiltrate. The plasma concentrationof N^G-N^G dimethyl-L-arginine (asymmetrical dimethylarginine,ADMA), an inhibitor of NOS, increased in end-stage uraemic patientsand was reduced by haemodialysis. However, the concentrationsreached in uraemic plasmas were lower than the ADMA ICM₅₀ ontEnd.1 NOS, indicating that this compound contributes with othermolecules to the inhibitory effect of uraemic plasma. Haemodialysisreduced also the enhanced effect exerted by some plasmas onNOS in J774. Therefore, the effect of endstage uraemic plasmaon NOS activity derive from the balance between inhibitors andactivators.     

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。     

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.     

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.     

单肺通气与一氧化氮

一氧化氮（nitric oxide，NO）是一种内皮源性舒张因子，具有松弛血管平滑肌、抑制血小板聚集和参与神经介质传递的主要信号转导等多种生物效应。内皮衍生的NO对维持正常的体循环和肺循环的血管紧张性起着重要作用。吸入NO可选择性地降低肺血管阻力、改善肺的氧合功能。内源性NO在单肺通气中对肺血流有重要的调节作用，理论上吸入NO能选择性舒张肺血管，对单肺通气中低氧血症具有治疗作用。现就近年来关于NO以及吸入NO在单肺通气中对肺血流调控等进展作一综述。     

Renal effects of inhaled nitric oxide in humans

We measured renal sodium and water excretion in five healthymale volunteers who inhaled nitric oxide. Urine volumes, urinarysodium and creatinine, and plasma sodium and creatinine weremeasured before, during and after a 2-h period inhaling nitricoxide (40 vpm in air). A control experiment, excluding the nitricoxide, was done on a separate day. Nitric oxide increased urinaryvolume (mean increase 85%, SEM 22%) and prevented a decreasein fractional excretion of sodium (32% SEM 8%) seen in the controlexperiments, without a detectable change in creatinine clearance.The results suggest the inhaled nitric oxide may alter tubularsalt and water resorbtion in humans. The mechanism for thisremains unclear. Br J Anaesth 2001; 86: 267–9     

Expression of nitric oxide and inducible nitric oxide synthase in acute renal allograft rejection in the rat

BACKGROUND: Recent studies have shown that nitric oxide (NO) synthases, particularly inducible nitric oxide synthase (i-NOS), are induced in acute rejection episodes following heart, liver, pancreas and kidney allotransplantation. Furthermore, tissue and cellular injury has been demonstrated to be mediated by peroxynitrite (ONOO-), a metabolite of NO as well as a potent oxidant. However, a detailed relationship between NO, i-NOS and graft injury in transplantation remains elusive. METHODS: The present study used the following models of renal transplantation in rats: allografts (n = 5, Brown-Norway to Lewis [LEW] rats), isografts (n = 5, LEW to LEW) and allografts treated with aminoguanidine (AG), an i-NOS inhibitor (n = 5). Blood urea nitrogen (BUN), serum creatinine (SCr) and urinary and serum nitrosocompounds (NOx) were measured on days 2, 4 and 7 post-transplant. Western blot analysis of i-NOS protein expression and measurement of i-NOS activity were carried out in grafts harvested on Day 7, along with immunohistochemical and histopathological examinations. RESULTS: In the allograft group, both BUN and SCr levels increased markedly on Day 7, in parallel with a sharp increase in NOx. A band stained by anti-i-NOS antibody was detected at approximately 130 kDa, along with high levels of i-NOS activity and diffusely distributed i-NOS-positive cells (macrophages). Histologically, an acute rejection episode was confirmed (Grade 3 according to Banff classifications). In the AG group, reduced renal function and graft injury were significantly less severe than in the allograft group. CONCLUSIONS: In rat renal allograft acute rejection, markedly increased levels of serum NOx were observed, along with enhanced tissue i-NOS activity, together resulting in graft injury. AG administration suppressed the increase of serum NOx levels, with concomitant mitigation of tissue injury and renal function impairment.     

Effect of nitric oxide predilution on inhaled nitrogen dioxide concentrations

We examined the possibility that predilution of a concentrated nitric oxide (NO) source with nitrogen, before contact with oxygen, can reduce the inspired nitrogen dioxide (NO2) concentration during administration of nitric oxide. A Manley Blease and a Siemens Servo 900 C ventilator delivered 10, 20, 40, 60 and 80 parts per million (ppm) NO using an NO source of 1000, 400 and 200 ppm. With the Manley Blease system, predilution from 1000 to 200 ppm NO reduced the inhaled NO2 concentration from 0.14 to 0.05 ppm (p < 0.01) at 10 ppm inhaled NO, and from 1.20 to 1.00 ppm (p < 0.01) at 40 ppm inhaled NO. With the Siemens Servo 900 C ventilator, inspiratory NO2 concentrations decreased from 0.21 to 0.11 ppm (p < 0.01) at 10 ppm inhaled NO, and from 1.49 to 1.16 ppm (p < 0.01) at 40 ppm NO. Predilution from 1000 to 400 ppm NO reduced the inspired NO2 concentrations by < 3% using either ventilator when the inspirated NO concentration was 80 ppm. Predilution of NO with nitrogen significantly reduced the inspired NO2 concentrations for nitric oxide concentrations between 10 and 40 ppm, but offered no clinically relevant advantage at higher NO concentrations.