NO—cGMP途径在嗜酸性粒细胞功能中作用的研究进展

一氧化氮是具有高度反应性的自由基 ,在体内广泛存在 ,是一种重要的细胞内信号转导分子 ,在细胞多种功能中起作用。NO主要通过提高环一磷酸鸟苷水平来实现其生物学功能。NO cGMP途径在嗜酸性粒细胞的功能中起重要作用 ,嗜酸性粒细胞在哮喘过程中能产生大量NO。两者之间存在密切联系。本文主要介绍NO cGMP信号转导通路、该通路在嗜酸性粒细胞趋化 ,凋亡等功能中作用以及NO释放在哮喘中意义的研究进展。     

NO及NO合成酶与感染性休克

感染性休克病理生理学过程十分复杂。NO在其中的作用既具有有害的一面，同时也存在有利的一面。受内毒素、细胞因子等诱导，iNOS表达上调并产生大量NO，引起循环衰竭、组织细胞损伤以及通过调节炎症介质基因表达扩大全身炎症反应。另一方面，eNOS所产生的NO对机体具有保护作用。然而，感染性休克时，eNOS蛋白质合成及其功能受到损害，反而成为血管内皮功能失常、诱发多器官功能障碍的重要原因。     

Effect of Insulin on NO Production by Monocytes from Patients with Metabolic Cardiovascular Syndrome

Parameters of NO metabolism in the gingiva were studied during experimental periodontitis accompanied by alloxan diabetes and exogenous hypercholesterolemia. We measured activities of inducible and constitutive NO synthase and concentrations of stable NO end metabolites in rat gingival tissue (total contents of nitrite and nitrate). Under pathological conditions NO metabolism significantly differed from the control. Treatment with mexidol for 14 days significantly decreased activity of inducible NO synthase in the gingiva of experimental animals. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 10, pp. 384–386, October, 2005     

TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection

To investigate the role of the Toll-like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2-, TLR4- and MyD88-deficient mice with the avirulent cyst-forming Fukaya strain of T. gondii. All TLR2- and MyD88-deficient mice died within 8 days, whereas all TLR4-deficient and wild-type mice survived after i.p. infection with a high dose of T. gondii. Peritoneal macrophages from T. gondii-infected TLR2- and MyD88-deficient mice did not produce any detectable levels of NO. T. gondii loads in the brain tissues of TLR2- and MyD88-deficient mice were higher than in those of TLR4-deficient and wild-type mice. Furthermore, high levels of IFN-gamma and IL-12 were produced in peritoneal exudate cells (PEC) of TLR4-deficient and wild-type mice after infection, but low levels of cytokines were produced in PEC of TLR2- and MyD88-deficient mice. On the other hand, high levels of IL-4 and IL-10 were produced in PEC of TLR2- and MyD88-deficient mice after infection, but low levels of cytokines were produced in PEC of TLR4-deficient and wild-type mice. The most remarkable histological changes with infiltration of inflammatory cells were observed in lungs of TLR2-deficient mice infected with T. gondii, where severe interstitial pneumonia occurred and abundant T. gondii were found.     

Coexistence of NMDA and AMPA receptor subunits with nNOS in the nucleus tractus solitarii of rat

We previously showed that most neuronal nitric oxide synthase (nNOS)-containing neurons in the nucleus tractus solitarii (NTS) contain NMDAR1, the fundamental subunit for functional N-methyl-D-aspartate (NMDA) receptors. Likewise, we found that almost all nNOS-containing neurons in the NTS contain GluR1, the calcium permeable AMPA receptor subunit. These data suggest that AMPA and NMDA receptors may colocalize in NTS neurons that contain nNOS. However, other investigators have suggested that non-NMDA receptors are located primarily on second-order neurons and NMDA receptors are located predominantly on higher-order neurons in NTS. We now seek to test the hypothesis that NMDA receptors, AMPA receptors and nNOS are colocalized in NTS cells. We performed triple fluorescent immunohistochemical staining of nNOS, NMDAR1 and GluR1, and performed confocal laser scanning microscopic analysis of the NTS. The distributions of nNOS immunoreactivity (IR), NMDAR1-IR and GluR1-IR in the NTS were similar to those we reported earlier. Superimposed images revealed that almost all NMDAR1-IR cells contained GluR1-IR and almost all GluR1-IR cells contained NMDAR1-IR. Some double-labeled cells were additionally labeled for nNOS-IR. All nNOS-IR neurons contained both GluR1-IR and NMDAR1-IR. These studies support our hypothesis that NMDA and AMPA receptors are colocalized in NTS neurons and are consistent with a role of both types of ionotropic receptors in transmission of afferent signals in NTS. In addition, these data provide support for an anatomical link between ionotropic glutamate receptors and nitric oxide in the NTS.     

Induction of NO synthesis in macrophages by Newcastle disease virus is associated with activation of nuclear factor-{kappa}B

Newcastle disease virus (NDV) has received much attention recentlybecause of its non-specific immune stimulating potential andits various anti-tumor activities. Here we describe that NDVinduces synthesis of NO and causes an activation of nuclearfactor-kB (NF-kB) In murine macrophages. These reactions werepart of an activation process which included also stimulationof adenosine deaminase and inhibition of 5'-nucleotidase. NDV-mediatedNO synthesis and NF-kB activation were blocked by an antioxidant(butylated hydroxyanisole), by an inhibitor of protein tyrosinekinase (genistein) and of protein kinase A (H-89), but not byan inhibitor of protein kinase C (staurosporin). These datasuggest that signalling requirements of NF-kB activation andNO production in NDV-treated macrophages are similar.     

pH and smooth muscle

In this paper, the control of vascular smooth muscle intracellular pH (pH_i) and the mechanisms of importance for the vasodilation to acidosis are reviewed. The three transport pathways of importance for the control of pH_i are a sodium-coupled bicarbonate transport, a Na,H-exchanger and a Cl,HCO₃^?exchange. While the two latter pathways are present in all smooth muscle cells studied, the sodium-coupled bicarbonate transport may be present in two forms which are either coupled to chloride efflux or are independent of chloride. The chloride-independent pathway seems electroneutral, indicating a 1:1 stoichiometry. All three transporters can be activated by vasoactive hormones and the second messengers involved are under intense investigation. With respect to the mechanisms involved in the vasodilation to acidosis, there seems to be a nitric oxide-dependent pathway as well as a direct effect of acidosis on the smooth muscle cells. In some preparations, prostanoids may also be involved. The direct vasodilator effect of acidosis is probably mediated through reduction of extracellular pH and the acidosis is associated with a reduction of the intracellular calcium concentration, which could explain the reduction of smooth muscle tone.     

肾素-血管紧张素-醛固酮系统、内皮素、一氧化氮在肾血管性高血压和肾上腺腺瘤中的临床意义

目的 :探讨肾素 -血管紧张素 -醛固酮系统、内皮素、一氧化氮在肾血管性高血压病人、肾上腺腺瘤病人中的作用和意义。方法 :采用放射免疫分析的方法测量所收集的经临床验证的肾血管性高血压病人(30例 )、肾上腺腺瘤病人 (35例 )和正常人 (35例 )的血清中肾素 (PRA)、血管紧张素Ⅱ (AⅡ )、醛固酮 (ALD)、内皮素 (ET)的含量 ,用酶法测定上述人群中的一氧化氮合酶 (Nitricoxidesynthase ,NOS)的含量来表示NO的量。结果 :对照组肾素、血管紧张素Ⅱ、醛固酮、内皮素、NOS分别为 (1 0 4± 0 90ng ml h ,71 0 6± 16 18pg ml,14 4 77±32 5 7pg ml,4 5 86± 2 0 85pg ml,32 2± 4 6 1U ml)。肾血管性高血压病人的血清中的肾素、血管紧张素Ⅱ、醛固酮、内皮素的含量分别为 (7 5 3± 2 2 3ng ml h ,14 4 77± 6 8 4 5pg ml,2 6 1 0 7± 73 0 3pg ml,96 72± 31 36pg ml)高于正常人 ,p <0 0 1,NOS(2 8 8± 6 14U ml) ,低于正常人 ,差别显著。肾上腺腺瘤病人肾素、血管紧张素Ⅱ、醛固酮、内皮素、NOS的含量分别为 (0 5 5± 0 4 7ng ml h ,5 1 85± 17 5 8pg ml,2 4 7 0 3± 84 0 3pg ml,81 83± 2 8 38pg ml,32 34± 9 0 2U ml) ;醛固酮、内皮素高于对照组 ,p <0 0 1,肾素、血管紧张素Ⅱ小于对     

Nitric oxide (NO) in expired air at rest and during exercise

Nitric oxide (NO) was analysed in expired air from 27 healthy human subjects. At rest the NO concentration was 10.5 ± 0.9 ng 1^-1 (mean ± SEM) corresponding to 8.6 ± 0.7 parts per billion (ppb). The expired NO concentration did not change when the subjects were switched from breathing NO-free tank gas to room air which contained 7.7 ng 1^-1 NO. Repeated measurements of expired NO with an interval of 1 day showed a mean variation of 2.2 ± 0.7ngl^-1 NO. The NO concentration in the first portion in the expired tidal volume (44%) was insignificantly higher than in the latter expired portion, 6.9 ± 1.9 vs. 5.1 ± 1.0 ng 1^-1 (n= 5). During moderately heavy exercise on an ergometer bicycle (90 W for women, n= 4, 150 W for men, n= 4) the expired concentration of NO decreased, however because of increased minute ventilation, the expired amount of NO almost doubled (from 111 ± 12 to 209 ± 30 ng min^-1). The source of the expired NO is not clear and both the airways and the pulmonary circulation may contribute.     

慢性丙型肝炎患者血清NO、NOS检测及其与内毒素的关系

目的:探讨了慢性丙型肝炎患者血清一氧化氮(NO)、一氧化氮酶(NOS)的含量变化及其与内毒素的关系.方法:分别应用酶法和比色法测定38例慢性丙型肝炎患者血清NO、NOS及内毒素的含量,并与35名正常健康人作比较.结果:慢性丙型肝炎患者血清NO、NOS和内毒素水平明显地高于正常人水平(P＜0.01)内毒素水平与NO水平呈明显正相关(r=0.7122,P＜0.01).结论:检测慢性丙型肝炎患者血清NO、NOS和内毒素水平对疾病的诊断、治疗是一个十分有用的检测指标.