一氧化氮合酶抑制剂氨基胍对脑缺血大鼠脑组织氨基酸含量的影响(英文)

目的 探讨氨基胍对大鼠脑缺血组织的保护作用及其作用机制。方法 采用线栓法复制大鼠中脑动脉梗死模型,缺血后给予氨基胍治疗。相应时间断头取脑,然后测定脑梗死体积、脑组织中氨基酸的含量。结果 脑梗死体积氨基胍组较缺血组明显缩小;缺血组比假手术组纹状体、海马、皮质中天门冬氨酸、谷氨酸、甘氨酸、GABA含量显著增加,给予氨基胍治疗后,天门冬氨酸、谷氨酸的含量明显降低,甘氨酸、GABA含量明显升高。结论 氨基胍降低脑组织中兴奋性氨基酸的含量。

一氧化氮合酶基因缺陷动物模型的应用研究进展

一氧化氮合酶基因缺陷动物模型的应用研究进展马子敏何子安（军事医学科学院卫生学环境医学研究所，３０００５０天津）关键词一氧化氮一氮化氮合酶一氧化氮合酶（ＮＯＳ）广泛存在于机体。它主要有三个类型：神经型ＮＯＳ（ｎＮＯＳ）、内皮型ＮＯＳ（ｅＮＯＳ）、诱导型...

一氧化氮与肿瘤

一氧化氮（ Ｎ Ｏ） 作为一种自由基性质的气体分子，参与了肿瘤的发生、发展、转移等过程。 Ｎ Ｏ 一方面介导了巨噬细胞、内皮细胞的杀瘤作用，另一方面又通过促进血管生成、增加血流量等促进肿瘤生长。对 Ｎ Ｏ 这种双向作用的深入研究，将为探索肿瘤的发生、发展和开辟新的治疗途径带来希望。

醒脑静注射液对脓毒症大鼠心肌线粒体氧化应激损伤的作用

目的:观察醒脑静注射液对脓毒症大鼠心肌线粒体氧化应激的影响。方法:以腹腔注射脂多糖(LPS)建立脓毒症模型,胃管注入醒脑静,将70只SD大鼠随机分为7组,每组10只:脓毒症6 h组(LPS 6h组)、LPS 24 h组、LPS 48 h组、醒脑静治疗6 h组(XNJ 6 h组)、XNJ 24 h组、XNJ 48 h组、对照组。观察各组不同时点心肌线粒体电镜下形态改变、半定量评分和超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、一氮化氮合酶(i NOS)水平的动态变化。结果 :醒脑静注射液可改善脓毒症大鼠心肌线粒体电镜下的形态改变,降低心肌线粒体电镜下的半定量评分,并可显著降低脓毒症大鼠心肌线粒体MDA、NO、i NOS水平和提高脓毒症大鼠心肌线粒体SOD水平。结论:脑静注射液可显著降低脓毒症大鼠心肌线粒体氧化应激的水平和提高清除氧自由基的能力,从而起到保护脓毒症大鼠心肌线粒体的作用。

L-硝基精氨酸对大鼠局灶性脑缺血损伤的保护作用及其机制

目的:研究非选择性一氧化氮合酶(NOS)抑制剂L-硝基精氨酸(L-NA)对局灶性脑缺血大鼠脑组织的保护作用及其机制。方法:线栓法复制大鼠大脑中动脉脑缺血模型;采用RT-PCR法检测大鼠缺血0,2,6,12,24 h脑组织中[内皮型NOS(eNOS)、神经型NOS(nNOS)及诱导型NOS(iNOS)]基因表达的变化;TTC染色法测定大鼠脑梗死体积,HPLC法测定纹状体、海马、皮层中氨基酸含量。结果:正常对照组可见eNOS和nNOS表达,eNOS于脑缺血后2 h达到高峰,nNOS于6 h达到高峰;正常对照组未见iNOS表达,但在脑缺血后开始表达,缺血后12 h达到高峰;缺血后12 h给予L-NA治疗3 dL-NA组中梗死体积/全脑体积(Ⅳ%)显著低于相应的缺血组;缺血组天门冬氨酸、谷氨酸、甘氨酸、GABA的含量明显高于假手术组,缺血12 h治疗3 d时,L-NA组中纹状体、海马、皮层中天门冬氨酸、谷氨酸的含量显著低于缺血组,GABA的含量显著高于缺血组,海马中甘氨酸含量显著高于缺血组。结论:缺血后期应用L-NA对脑缺血有治疗作用,可能与兴奋性氨基酸合成、释放相对减少,抑制性氨基酸合成、释放相对增加有关。

L-硝基精氨酸对局灶性脑缺血大鼠脑组织氨基酸含量的影响

目的:观察一氧化氮合酶(NOS)抑制剂L-硝基精氨酸(L-NA)对脑缺血大鼠纹状体、海马、皮质中天冬氨酸、谷氨酸、甘氨酸、γ-氨基丁酸(GABA)含量的影响,探讨L-NA对大鼠脑缺血组织的保护作用及其作用机制。方法:采用线栓法复制大鼠大脑中动脉梗塞(MCAO)模型,缺血后给予L-NA治疗。相应时间断头取脑,然后测定脑梗死体积、脑组织中氨基酸的含量。结果:脑梗死体积L-NA组较缺血组明显缩小;与假手术组比较,缺血组大鼠纹状体、海马、皮质中天冬氨酸、谷氨酸、甘氨酸、GABA含量显著增加,给予L-NA治疗后,缺血后12 h治疗组中天冬氨酸、谷氨酸的含量明显降低,甘氨酸、GABA含量明显升高。结论:L-NA降低脑组织中兴奋性氨基酸的含量及升高抑制性氨基酸的含量可能是保护脑缺血的重要机制。

NO、NOS在早期糖尿病肾病大鼠血清中的变化

目的观察早期糖尿病肾病大鼠血清中一氧化氮(NO)、一氮化氮合酶(NOS)的变化。方法将20只健康雄性大鼠随机分为正常对照组和糖尿病组,每组10只。糖尿病组大鼠采用链脲佐菌素诱导糖尿病模型。第10周末测定2组血糖、肾重/体质量2、4 h尿蛋白定量;检测各组血清NO含量及总一氧化氮合酶(T-NOS)、诱导型一氧化氮合酶(iNOS)和结构型一氧化氮合酶(cNOS)活性。结果糖尿病组血糖、肾重/体质量、24 h尿蛋白定量、NO水平及T-NOSi、NOS活性均较正常对照组明显增加(均P<0.01);cNOS活性2组间比较无显著差异(P>0.05)。结论早期糖尿病肾病大鼠血清NO含量和iNOS活性明显升高。

Enhanced visible-light photo-oxidation of nitric oxide using bismuth-coupled graphitic carbon nitride composite heterostructures

Pure bismuth（Bi） metal-modified graphitic carbon nitride（g-C3N4） composites（Bi-CN） with a pomegranate-like structure were prepared by an in situ method.The Bi-CN composites were used as photocatalysts for the oxidation of nitric oxide（NO） under visible-light irradiation.The inclusion of pure Bi metal in the g-C3N4 layers markedly improved the light absorption of the Bi-CN composites from the ultraviolet to the near-infrared region because of the typical surface plasmon resonance of Bi metal.The separation and transfer of photogenerated charge carriers were greatly accelerated by the presence of built-in Mott-Schottky effects at the interface between Bi metal and g-C3N4.As a result,the Bi-CN composite photocatalysts exhibited considerably enhanced efficiency in the photocatalytic removal of NO compared with that of Bi metal or g-C3N4 alone.The pomegranate-like structure of the Bi-CN composites and an explanation for their improved photocatalytic activity were proposed.This work not only provides a design for highly efficient g-C3N4-based photocatalysts through modification with Bi metal,but also offers new insights into the mechanistic understanding of g-C3N4-based photo catalysis.

Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury

Inducible heat shock protein 70 kD (HSP-70i) has been shown to protect cells, tissues, and organs from harmful assaults in in vivo and in vitro experimental models. Hemorrhagic shock followed by resuscitation is the principal cause of death among trauma patients and soldiers in the battlefield. Although the underlying mechanisms are still not fully understood, it has been shown that nitric oxide (NO) overproduction and inducible nitric oxide synthase (iNOS) overexpression play important roles in producing injury caused by hemorrhagic shock including increases in polymorphonuclear neutrophils (PMN) infiltration to injured tissues and leukotriene B4 (LTB4) generation. Moreover, transcription factors responsible for iNOS expression are also altered by hemorrhage and resuscitation. It has been evident that either up-regulation of HSP-70i or down-regulation of iNOS can limit tissue injury caused by ischemia/reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of ansamycin family, has been shown to induce HSP-70i overexpression and then subsequently to inhibit iNOS expression, to reduce cellular caspase-3 activity, and to preserve cellular ATP levels. HSP-70i is found to couple to iNOS and its transcription factor. Therefore, the complex formation between HSP-70i and iNOS may be a novel mechanism for protection from hemorrhage/resuscitation-in-duced injury.

Polypeptide from Chlamys farreri inhibits UVB-induced apoptosis of HaCaT cells via iNOS/NO and HSP90

Polypeptide from Chlamys farreri(PCF) is a novel marine bioactive product that was isolated from the gonochoric Chinese scallop Chlamys farreri,and was found to be an effective antioxidant in our recent studies.In this study,we investigated the effect of PCF on ultraviolet B(UVB)-induced apoptosis of HaCaT cells and the intracellular signaling pathways involved.Pretreatment with the inducible nitric oxide synthase(iNOS) inhibitor S-methylisothiourea sulfate inhibited UVB-induced apoptosis,indicating that iNOS and NO play important roles in apoptosis.On the other hand,the inhibition of UVB-induced apoptosis in the immortalized keratinocyte(HaCaT) cells by PCF was estimated using a DNA ladder.PCF treatment inhibited UVB-induced iNOS activation,as determined by RT-PCR,NO production,as determined by ESR,and up-regulated heat shock protein(HSP) 90 activation,as determined by Western blotting.Our results indicate that iNOS and NO are involved in UVB-induced apoptosis of HaCaT cells and the protective effect of PCF against UVB irradiation is exerted by suppressing the expression of iNOS,followed by inhibition of NO release and enhanced activation of HSP90.

Comparison of Urea-Derived N_2O Emission from Soil and Soil-Plant System

A pot experiment with a sandy loam soil and spring wheat as test crop was conducted to compare the N2O emission from soil system with plant cut off and from soil-plant system with plant kept. The results showed that after urea fertilizer applied, the N2O emission from soil and soil-wheat system decreased exponentially with time, and its total amount was 0.34%~0.63% and 0.33%~0.58% of applied urea-N respectively, no significant difference being found between these two systems. The N2O emission had a very significant negative relationship (P = 0.01) with the biomass of wheat plant. A combined application of urease inhibitor hydroquinone and nitrification inhibitor dicyandiamide could reduce the N2O emission by 50%~83% and 46%~74%, respectivelyl from soil and soil-wheat system. The N2O was mainly produced and emitted from soil, and the soil biochemical regulation, i.e., applying related inhibitors into soil could effectively diminish the urea derived N2O emission.

N Cycle, N Flow Trends in Japan, and Strategies for Reducing N_2O Emission and NO_3^- Pollution

To feed an increasing population, large amounts of chemical nitrogen fertilizer have been used to produce much of our food, feed and fiber thereby increasing nitrogen levels in soils, natural waters, crop residues, livestock wastes,and municipal and agricultural wastes, with national and international concern about its potential adverse effects on environmental quality and public health. To understand these phenomena and problems, first the nitrogen cycle and the environment are described. Then recent trends for nitrogen cycling through the food and feed system, N2O emissions from fertilized upland and paddy soils, and NO-3 pollution in ground water in Japan are reported. Finally, mitigation strategies in Japan for reducing N2O emission and NO-3 pollution are proposed, including nitrification inhibitors, controlled release fertilizers, utilization of plant species that could suppress nitrification, utilizing the toposequence, government policy, and appropriate agricultural practices. Of all the technologies presented, use of nitrification inhibitors and controlled release fertilizers are deemed the most important with further development of these aspects of technologies being expected. These practices, if employed worldwide, could help reduce the load, or environmental deterioration, on the Earth's biosphere.

NITRIC OXIDE SYNTHESIS IN MYOCARDIUM FOLLOWING BURN INJURY IN RATS

The nitric oxide and cyclic GMP production in myocardium early after burn injury in rats were investi- gated. Nitric oxide synthase activity was measured in cytosols from the left ventricular wall of burned rats. Cytosols from the control group animals were shown to contain mainly Ca2+ dependent nitric oxide synthase （cNOS） with small amount of Ca2+ independent nitric oxide synthase （iNOS）. Following burn injury, there was a marked increase in iNOS activity with a peak at sh post-burn, however, myocardial cNOS ac- tivity was found to decline obviously. Parallel to iNOS induction there was a significant increase in myocar- dial nitric oxide and cyclic GMP production. All these changes were alleviated by treatment of the rats with dexamethasone. Since increases in cyclic GMP levels in the heart were associated with reduced myocardial contractility, it is possible that enhanced production of nitric oxide by a Ca2+, independent NO synthase ac- counts, at least in part, for the depression of myocardial contractility seen in burn animals and patients.

良性前列腺增生组织中一氧化氮合酶活性的变化

为探讨一氧化氮（ＮＯ）与良性前列腺增生（ＢＰＨ）发病的关系，应用双波长分光光度法测定１５例正常前列腺及２５例ＢＰＨ组织中一氧化氮合酶（ＮＯＳ）活性，并比较不同年龄组的正常前列腺及ＢＰＨ组织中ＮＯＳ活性水平。结果：ＢＰＨ组织中ＮＯＳ活性（９６．７７±２８．０２ｐｍｏｌ．ｍｇ－１．ｍｉｎ－１）明显低于正常前列腺者（２９０．９９±１３０．６８ｐｍｏｌ．ｍｇ－１．ｍｉｎ－１），Ｐ＜０．００１。不同年龄组的正常前列腺组织中ＮＯＳ活性水平与年龄无相关关系。而在５０岁、６０岁和≥７０岁三个年龄组之间的ＢＰＨ组织中ＮＯＳ活性水平有显著性差异，Ｐ＜０．０１，ＢＰＨ组织中ＮＯＳ活性水平随年龄增大呈下降趋势。结果提示前列腺组织中ＮＯＳ活性水平与ＢＰＨ有相关关系，ＮＯＳ活性降低可能是ＢＰＨ的年龄依赖性发病原因之一。

急性结石性胆囊炎与一氧化氮、氧化和脂质过氧化关系的研究

目的 从自由基医学的角度探讨一氧化氮、氧化和脂质过氧化与急性结石性胆囊炎之间的关系。方法 用分光光度法检测了 97例急性结石性胆囊炎患者 (ALC)和 10 0例健康志愿者 (HVT)血浆中的一氧化氮 (P NO)、维生素C (P VC)、维生素E (PVE)、β 胡萝卜素(P β CAR)和过氧化脂质 (P LPO)含量及红细胞超氧化物歧化酶 (E SOD)、过氧化氢酶 (E CAT)、谷胱甘肽过氧化物酶 (E GSH Px)活性和过氧化脂质 (E LPO)含量 ,分析比较了ALC组与HVT组各平均检测 (AV)之间的差异及患者组手术前后各AV之间的差异。结果 与HCT组上述各AV比较 ,ALC组P NO、P LPO和E LPO的AV均显著增高 (P =0 0 0 1) ,P VC、P VE、P β CAR、E SOD、E CAT和E GSH Px的AV均显著降低 (P =0 0 0 0 1) ;与ALC组手术前上述各AV比较 ,ALC组手术后P NO、P LPO和E LPO的AV均显著降低 (P <0 0 0 1) ,P VC、E SOD、E CAT和E GSH Px的AV均显著增高 (P<0 0 0 1) ,但PVE和P β CAR的AV在手术前后无显著性差异 (P >0 0 5 )。结论 ALC患者体内的一氧化氮代谢严重紊乱 ,一系列自由基连锁反应病理性加剧 ,氧化抗氧化平衡严重失调。

慢性乙型肝炎肝组织内NO合成酶及其意义

目的和方法用四氮唑兰（ＮＢＴ）组化法检测１４份ＨＢＶ感染引起的慢性肝炎、肝硬化、肝衰竭病人肝组织中一氮化氮合酶（ＮＯＳ）的活性。结果及结论慢性肝炎及活动性肝硬化病人肝组织内ＮＯＳ活性明显增强，主要分布在肝细胞及胆管样上皮细胞内；肝细胞坏死及纤维组织分布区域ＮＯＳ活性低或不能测出；肝衰竭尸检肝组织内ＮＯＳ活性显著降低。肝组织内ＮＯＳ含量与Ｋｎｏｄｅｌｌ评分呈负相关（ｒ＝－０．８７，Ｐ＜０．０１）。

硝酸酯偶联药物的研究进展

一氧化氮作为体内重要的信使分子和功能分子,参与众多的生理病理过程。随着对体内一氧化氮功能的研究与认识的深入,出现了新型的硝酸酯与非甾体抗炎药、糖皮质激素及熊去氧胆酸等相偶联的药物,本文就此类药物的研究背景、作用机制及临床应用前景等作一综述。

Oral arginine improves linear growth of long bones and the neuroendocrine mechanism

Objective To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide （NO）-cyclic guanosine monophosphate （cGMP） pathway. Methods Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water （0.045 g L-arginine was mixed with 1 mL water） and administered in rats （10 mL/kg） through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteo- clast surface of the femur. Serum growth hormone （GH） concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase （nNOS）, soluble guanylyl cyclases （sGCal and sGCfll）, growth hormone-releasing hormone （Ghrh） and somatostatin （SS） in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels ofnNOS, sGCα1 and sGCβ1 in hypothalamus. Results After treat- ment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased （P 〈 0.05）, and serum GH concentration was elevated （P 〈 0.05）. Besides, mRNA and protein levels ofnNOS and sGCα1 （P 〈 0.05）, as well as the expression of Gh mRNA （P 〈 0.01）, were significantly up-regulated, while the expression of SS mRNA was down- regulated （P 〈 0.05）. Conclusion Oral administration ofarginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.

Nitric oxide synthase gene expression in injured spinal cord tissue

OBJECTIVE: To investigate gene expression of three nitric oxide synthase isozymes in injured spinal cord tissue. METHODS: Thirty-six adult SD rats were randomly divided into six groups: a normal group and five injury groups, with six per each group. Animals in the injury groups were sacrificed at 2, 6, 12, 24, 48 h after injury. A compression injury model on the spinal cord was made according to Nystrom B et al and gene expression of the three NOS isozymes were examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Gene expression of nNOS and eNOS were detectable in the normal group and were up-regulated quickly after injury, reaching a maximum at 6 h: (0.633 +/- 0.012) and (1.236 +/- 0.207). Gene expression of iNOS was detectable only in the injury groups and it was gradually up-regulated after injury, reaching a maximum at 24 h: (1.043 +/- 0.049). CONCLUSION: Injury to the spinal cord leads to early up-regulation of cNOS and late up-regulation of iNOS. Different NOS isozymes may play different roles in secondary spinal cord injury.

Effect of Acupuncture on NO, NOS and Ca^(2+)-Mg^(2+)-ATPase Activity in Brain Tissue of Subacute Aging Rats Induced by D-galactose

Objective： To explore the mechanism of acupuncture in treating brain aging. Methods： Forty healthy Wistar rats were randomly divided into 4 groups with 10 rats in each group. The rats in the control group didn＇t received modeling and treatment. The rats in the model group, the Governor Vessel acupoints group （GVA group） and the body acupoints group （BA group） were induced as subacute aging rat model. The rats in the model group didn＇t take treatment. On the modeling day, the rats in the GVA group received acupuncture at Baihui （GV 20） and Dazhui （GV 14） while the rats in the BA group received acupuncture at Guanyuan （CV 3） and Zusanli （ST 36）. The contents of NO and NOS, as well as the activity of Ca^2＋-Mg^2＋-ATPase in the brain tissue of rats in each group were observed. Results： After modeling, the contents of NO and NOS of brain tissue increased significantly and the activity of Ca2^＋-Mg^2＋-ATPase decreased markedly. Acupuncture treatment could inhibit the increases of NO and NOS contents, improve the decrease of the activity of Ca^2＋-Mg^2＋-ATPase. The results of the GVA group were better than those of BA group （both P〈0.05）. Conclusion： Acupuncture improved the activity of Ca^2＋-Mg^2＋-ATPase and stabilized the NOS concentration. As a result, the NO content was balanced and the ohvsiological function of NO was fully induced for anti-a^in~, esoeciallv in the GVA group.