牛磺酸对失血性休克复苏家兔血浆和心肌NOS活性影响

目的:探讨牛磺酸对失血性休克复苏后血浆和心肌一氧化氮合酶(NOS)活性、一氧化氮(NO)含量变化的影响.方法:新西兰种兔24只随机分为3组(n=8):对照组、休克组、牛磺酸治疗组.采用失血性休克复苏动物模型.连续观察休克前、休克1.5 h、复苏后1 h、2 h、3 h血浆一氧化氮合酶(NOS)活性、一氧化氮代谢产物(NO-2/NO-3)含量、乳酸脱氢酶(LDH)活性的动态变化.测定复苏后3 h心肌一氧化氮合酶(NOS)活性、一氧化氮代谢产物(NO-2/NO-3)含量的变化,并常规留取心肌标本观察形态学改变.结果:①休克组复苏后各时限血浆NOS活性、NO-2/NO-3含量、LDH活性显著高于休克前及休克1.5 h;②休克组复苏后3 h心肌NOS活性、NO-2/NO-3含量显著高于对照组,心肌出现明显水肿和脂肪变性;③牛磺酸(40 mg·kg-1 iv)可显著缓解上述变化.结论:失血性休克复苏后NOS的激活和NO的大量释放,可能介导了休克复苏所致心肌损伤,牛磺酸可减少NO的生成使心肌损伤减轻.     

双歧杆菌对菌群失调大鼠血清NO及NOS的影响

目的观察双歧杆菌对抗生素诱导的菌群失调大鼠血清一氧化氮(Nitricoxlcle,NO)及一氧化氮合成酶(Nitric oxide synthase,NOS)的影响。方法肠道盐酸林可霉素脱污染制备肠道菌群失调大鼠。造模成功后用双歧杆菌活菌灌胃治疗,14 d后血清学检测细胞因子NO、NOS水平。结果与模型组相比,NO含量明显增多(P<0.05);NOS含量降低(P<0.05)。结论双歧杆菌活菌可能通过调节细胞因子NO、NOS含量而调整菌群失调大鼠肠道内有益菌的比例。     

口服L-瓜氨酸对大鼠勃起功能的影响

给予雄性SD大鼠口服不同剂量组的L-瓜氨酸8周后,检测电刺激大鼠阴茎海绵体神经海绵体内压(ICP)的变化;比色法检测血清和组织中的一氧化氮(NO)含量、一氧化氮合酶(NOS)活性及血清中超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)含量等。结果高剂量(4.5 g.kg-1)L-瓜氨酸组ICP、NO含量、NOS活性显著增高;低、高剂量组SOD活性、GSH含量变化差异均无显著性。     

血立停胶囊对早孕大鼠RU486药流后NO、NOS表达的影响

目的:研究血立停胶囊对早孕大鼠RU486药物流产后的子宫平滑肌一氧化氮(NO)及一氧化氮合酶(NOS)水平变化的影响。方法:选择妊娠Wistar大鼠,随机分为5组,即对照组,米非司酮组,大剂量血立停组,小剂量血立停组,催产素组。于妊娠第7天,开始相应处理,妊娠第14天分别监测早孕大鼠RU486药物流产后的子宫平滑肌一氧化氮(NO)及一氧化氮合酶(NOS)水平后处死。结果:大剂量血立停可明显降低大鼠子宫肌组织匀浆中NO、NOS含量,与对照组比较差异有显著性(P<0.05)。结论:血立停胶囊可降低子宫肌组织匀浆中NO、NOS水平,从而起到对药物流产后阴道出血的治疗作用。     

核因子κB在精氨酸血管升压素诱导大鼠心肌成纤维细胞一氧化氮合成中的作用

本文探讨了精氨酸血管升压素(AVP)刺激下体外培养的大鼠心肌成纤维细胞(CFs)内一氧化氮(NO)含量、一氧化氮合酶(NOS)活性、诱导型一氧化氮合酶基因表达的变化及其与核因子κB(NF-κB)的关系。用胰酶消化法分离培养Sprague Dawley仔鼠的CFs,分别采用硝酸还原酶法、分光光度法、逆转录-聚合酶链式反应(RT-PCR)、免疫荧光-共聚焦显微镜和蛋白质印迹检测AVP干预下CFs的NO含量、NOS活性、iNOS mRNA表达和NF-κB的活化。结果显示,AVP浓度依赖性(0．001—0．1μmol／L)地增加CFs的NO含量,提高NOS活性,增加iNOS mRNA表达;AVP能够活化NF—κB,使其由细胞浆转位于细胞核;NF-κB特异性抑制剂吡咯啉烷二甲基硫脲(PDTC)能够抑制AVP诱导的CFs NO含量增加、NOS活性提高和iNOS mRNA表达增加。上述结果提示,AVP干预下CFs iNOS mRNA表达增加、NOS活性增高、NO合成增多可能通过NF-κB激活途径,NF-κB激活参与心肌纤维化的发生和发展。     

心肌缺血后处理中一氧化氮的变化

目的:研究心肌缺血再灌注与心肌缺血后处理两种因素下大鼠心肌一氧化氮(NO)的含量与一氧化氮合酶(niricoxide synthase,Nos)活性的关系.方法:采用健康雄性Wistar大鼠(n=12)建立离体心肌缺血再灌注损伤模型.采用高效液相色谱仪(HPLC)直接测定心脏灌流液中NO的含量.采用高效液相色谱仪(HPLC)测定瓜氨酸生成量计算心肌中NOS活性.使用紫外分光光度法测定乳酸脱氢酶(LDH)活性.使用染色法计算心肌梗死面积.结果:平衡末,对照组NO含量与实验组NO含量差异无统计学意义(P>0.05);对照组平衡末NO含量与再灌注后NO含量差异无统计学意义(P>0.05);对照组再灌注后NO含量与实验组后处理后NO含量相比差异有统计学意义(P<0.05);实验组后处理后NO含量与平衡末NO含量相比显著升高(P<0.05).实验组后处理后心肌组织NOS活性明显高于对照组(P<0.05).实验组心肌释放的LDH活性显著低于对照组(P<0.01).与对照组比较,缺血后处理可减少心肌梗死面积(P<0.05).结论:缺血后处理时心肌细胞中NO生成量与NOS活性普遍高于缺血再灌注时.     

银杏叶提取物对糖尿病大鼠心肌损伤的防护作用

目的:研究银杏叶提取物(EGb)对糖尿病大鼠心肌的防护作用.方法:用光镜和透射电镜观察EGb对糖尿病大鼠心肌的形态学改变,并测定心肌组织内超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)、结构型一氧化氮合酶(cNOS)、诱导型一氧化氮合酶(iNOS)的活性及一氧化氮(NO)、丙二醛(MDA)的含量.结果:糖尿病大鼠心肌光镜下主要表现为心肌细胞空泡变性及心肌纤维局灶性溶解;电镜下主要表现为心肌线粒体肿胀,嵴变短,肌原纤维溶解;SOD活性下降,NOS、iNOS活性及MDA、NO含量增高.EGb治疗组病变明显减轻,EGb治疗组心肌组织内SOD活性明显高于糖尿病组,NOS、iNOS活性及MDA、NO含量低于糖尿病组.结论:EGb可能通过抗脂质过氧化作用和降低NO水平而对糖尿病心肌产生保护作用.     

NR和NOS在CTK延缓离体小麦叶片衰老中的作用

用一氧化氮(NO)清除剂血红蛋白(Hb)、硝酸还原酶(NR)抑制剂钨酸钠(Na2WO4)、一氧化氮合酶(NOS)抑制剂L-硝基精氨酸甲酯(L-NAME)并结合激动素(KT)和玉米素(ZT)两种细胞分裂素(CTK)处理离体小麦叶片,测定分析各处理的相关生理生化指标,以明确NR和NOS在CTK延缓离体小麦叶片衰老过程中的作用.结果显示:KT和ZT单独处理均能显著延缓离体小麦叶片衰老过程中叶绿素、可溶性蛋白含量的降低,抑制丙二醛(MDA)的积累,促进NR和NOS活性升高;在Hb、Na2WO4或L-NAME存在时,上述KT和ZT延缓衰老的效应均显著减弱,同时NR和NOS活性的升高也分别被Na2WO4和L-NAME显著抑制.该结果暗示CTK延缓离体小麦叶片衰老可能与其诱导了NR和NOS活性的提高,进而促进NO的生成有关.     

大鼠脑缺血／再灌注损伤中一氧化氮和一氧化氮合酶的变化

目的:探讨脑缺血/再灌注损伤中脑组织一氧化氮和一氧化氮合酶的变化.方法:用线栓法建立大脑中动脉梗死(MCAO)模型,观察局灶性脑缺血30 min再灌注30 min、1 h、3 h、 6 h、12 h、24 h、48 h 、72 h、96 h、168 h NO含量和NOS活性的变化.结果:脑缺血/再灌注过程中NO含量和NOS活性呈"双峰样"改变.缺血/再灌注30 min后NO含量和NOS活性升高,再灌注3 h时NO含量和NOS活性下降,再灌注6 h、12 h、24 h、48 h 、72 h NO含量和NOS活性再次显著升高,与再灌注72 h达峰值.结论:NO和NOS通过多种途径参与了脑缺血/再灌注损伤的病理过程.     

一氧化氮合酶的若干研究进展

一氧化氮合酶(NOS)是一氧化氮(NO)生物学与医学研究的重要内容.近年来,对NOS酶本质及其生化与分子生物学特性甚至某些分子遗传学方面的认识都在迅速发展和深化.研究表明,干预NOS-NO途径的某些环节,如酶激活、NO合成、释放与转运甚至有关酶的编码基因及其表达,将为某些临床问题的解决提供新的思路和手段．     

Beneficial effect of gaseous nitric oxide on the healing of skin wounds

Intermittent daily exposures (60 s) to NO-containing gas flow (NO dose of 500 ppm) generated by air-plasma unit "Plason" improves healing of skin wounds in rats. The gas flow treatment shortened the recovery time of both aseptic and purulent wounds (300 mm2 area) by nearly a third. The treatment allows to achieve a marked improvement in the histological, histochemical, and electron-microscopic characteristics of the affected tissue. The mechanism of this phenomenon was studied by spin trapping method. The NO status of the wound tissue was investigated with EPR by following the formation of paramagnetic mononitrosyl complexes with iron-diethyldithiocarbamate, or with the heme groups in hemoglobin or myoglobin. For the first 5 min after a gas treatment with the exposure of 60s, detectable NO levels in the affected tissue were slightly lowered with respect to untreated controls. At subsequent times, treated tissues showed the formation of large quantities of nitroso-iron complexes: At 30-40 min after gas exposure, their levels were nearly two orders of magnitude higher than soon after (15 s-5 min) the exposure. The data demonstrate that the accumulation of nitrosyl-iron complexes reflects a sharp rise in endogenous NO production inside the affected tissue. Paradoxically, the beneficial effect of gaseous NO treatment can be mediated by the formation of limited quantities of peroxynitrite due to the reaction between exogenous NO and superoxide anions generated in high amount in wound tissue. This peroxynitrite has a strong prooxidant effect and can activate various antioxidant systems which diminish the amount of superoxide anions in wound tissue. The reduced superoxide levels allow to increase the contents of endogenous NO in gas-treated tissues. Therefore, the beneficial action of the treatment is attributed to enhanced NO bioavailability.     

Distribution and Significance of Nitric Oxide Synthase in Brain Tissues of Rats Exposed to Deltamethrin Insecticide

The distribution of nitric oxide synthase(NOS)in brain tissues of rats exposed to deltamethrininsecticide has been examined by histochemical NADPH-diaphorase staining techniques on frozen sec-tions.After injection of deltamethrin(12.5mg/kg,i.p.),a reproducible sequence of toxic signs ofhyperexcitability were elicited.The observation and image analysis showed that,within brain sec-tions of rats exposed to deltamethrin,the numbers and the total staining areas of the NOS positiveneurons were greatly increased,especially in cerebral cortex,hippocampal formation and paraventric-ular nucleus.In addition,the density of single neuron and the processes were also increased.The re-sults suggested that deltamethrin may induce the NOS expression or activate the NOS activity.TheNOS activation may involve in the chains responsible for the excitatory neurotoxicities induced bydeltamethrin.     

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS)

By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8.     

软体动物的一氧化氮及其合酶的研究进展

一氧化氮作为一种重要的信息分子,参与调节软体动物的嗅觉、运动、取食、机体防御及学习行为。本文从生理、生化、形态定位以及信号转导几方面综述了有关软体动物一氧化氮及其合酶的最新研究进展。     

Effect of l-Arginine Analogs and a Calcium Chelator on Nitric Oxide (NO˙) Production by Leishmania sp.

Leishmania amazonensis, L. braziliensis and L. chagasi promastigotes were grown in the presence of l-arginine analogs such as Nω-nitro-l-arginine methyl ester (l-NAME), NG-nitro-l-arginine (l-NNA) and d-arginine (an inactive l-arginine isomer), besides an intracellular calcium chelator [ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetra acetic acid; EGTA] to verify the importance of l-arginine metabolism and the cofactors for these parasites. The parasite's growth curve was followed up and the culture supernatants were used to assay nitric oxide (NO˙) production by the Griess reaction. The results showed a significant effect of l-arginine analogs on NO˙ production by all Leishmania species studied, especially l-NAME, an irreversible inhibitor of the constitutive nitric oxide synthase (cNOS). When L. amazonensis promastigotes were pre-incubated with l-NAME, the infection range of the murine macrophages was lowered to 61% in 24?h and 19% after 48?h. These data demonstrated that the parasite NO˙ pathway is important to the establishment of the infection.     

Analysis of the effects of nitric oxide and oxygen on nitric oxide production by macrophages

The interactions between NO and O(2) in activated macrophages were analysed by incorporating previous cell culture and enzyme kinetic results into a novel reaction-diffusion model for plate cultures. The kinetic factors considered were: (i) the effect of O(2) on NO production by inducible NO synthase (iNOS); (ii) the effect of NO on NO synthesis by iNOS; (iii) the effect of NO on respiratory and other O(2) consumption; and (iv) the effects of NO and O(2) on NO consumption by a possible NO dioxygenase (NOD). Published data obtained by varying the liquid depth in macrophage cultures provided a revealing test of the model, because varying the depth should perturb both the O(2) and the NO concentrations at the level of the cells. The model predicted that the rate of NO(2)(-) production should be nearly constant, and that the net rate of NO production should decline sharply with increases in liquid depth, in excellent agreement with the experimental findings. In further agreement with available results for macrophage cultures, the model predicted that net NO synthesis should be more sensitive to liquid depth than to the O(2) concentration in the headspace. The main reason for the decrease in NO production with increasing liquid depth was the modulation of NO synthesis by NO, with O(2) availability playing only a minor role. The model suggests that it is the ability of iNOS to consume NO, as well as to synthesize it, that creates very sensitive feedback control, setting an upper bound on the NO concentration of approximately 1 microM. The effect of NO consumption by other possible pathways (e.g., NOD) would be similar to that of iNOS, in that it would help limit net NO production. The O(2) utilized during enzymatic NO consumption is predicted to make the O(2) demands of activated macrophages much larger than those of unactivated ones (where iNOS is absent); this remains to be tested experimentally.     

生物喋呤的生物学效应及其在脓毒症中的意义

研究表明,一氧化氮（ＮＯ）的过度产生可能是诱发脓毒性休克的最后共同通路,而生物喋呤为一氧化氮合酶（ＮＯＳ）重要的辅因子。多种免疫刺激因子均可诱导细胞内ＢＨ４合成显著增加,其可瑟ＮＯＳ紧密结合,调控ＮＯ的合成与释放。本文讨论了ＢＨ４的生物学效应,调控机制及其在脓毒症中的作用,并简要介绍其合成抑制剂在脓毒症防治中的潜在意义。     

一氧化氮与肺纤维化的研究进展

肺纤维化是一组由多种因素引起的肺间质性病变,肺纤维化的发病机制迄今尚未完全清楚。近年来,发现在哺乳动物细胞的一氧化氮合酶催化合成的一氧化氮在肺纤维化的发生发展中发挥着重要的作用。因此,阐述一氧化氮与肺纤维化的关系,有着重要的理论意义和潜在的临床应用价值。