癫痫发作后脑内一氧化氮、一氧化氮合酶及相应氨基酸的变化

目的　探讨NO在癫痫的病理生理过程中的作用及可能作用机制。方法　将大鼠随机分为对照组 ,实验性癫痫组 ,L 硝基精氨酸甲酯 (L NAME)抑制组 ,分别取双侧海马及颞叶皮层组织测定NO ,NOS及相应氨基酸的含量。结果　致痫后NOS活性上升 >50 %。NO含量明显上升 ,60分钟组NO含量明显下降。L Arg,Glu含量均显著上升。GABA则明显下降。不同剂量的L -NAME均抑制痫性发作及相应指标的变化。癫痫患者脑脊液中NO ,NOS含量均较对照组明显上升。结论　NO参与癫痫发生的机制 ,但对其维持作用并不重要。其致痫机制仅部分与兴奋性氨基酸有关。     

癫痫患儿血清一氧化氮和一氧化氮合酶含量的变化及意义

目的　探讨癫疒间 患儿血清一氧化氮 (NO)、一氧化氮合酶 (NOS)的变化及意义。方法　利用ELISA方法 ,测定 5 8例癫疒间 患儿 (癫疒间 组 )和 2 3名健康儿童 (对照组 )血清中NO、NOS的含量 ,并分组比较不同条件下其含量的变化。结果　癫疒间 组血清NO、NOS的含量分别为 (5 .86± 1.2 1) μmol/ml和 (2 8.2 6± 8.4 9)U/ml,较对照组的 (3.78± 0 .74 ) μmol/ml及 (17.86± 4 .5 8)U/ml明显升高 (P <0 0 1) ;发作近期为 (7.31± 1.2 7)μmol/ml和 (31.2 5± 11.35 )U/ml,明显高于发作间期 (4 .2 7± 0 .6 6 ) μmol/ml和 (2 4 .15± 7.85 )U/ml(P <0 0 1) ;癫疒间 组EEG异常者为 (7.18± 1.35 ) μmol/ml和 (34.4 8± 8.5 6 )U/ml,明显高于EEG正常者 (4 .0 4± 0 .75 ) μmol/ml和 (2 2 .85± 7.4 5 )U/ml(P <0 0 1) ;但与发作类型、病程及是否接受治疗无关 (P >0 0 5 )。结论　癫疒间 发作近期血中NO、NOS生成增加 ,NO作为内源性调质参与癫疒间 发作病理生理过程     

一氧化氮和一氧化氮合酶在鼠脑内形成吗啡依赖的作用研究

目的：研究一氧化氮（NO）和一氧化氮合酶（NOS）在吗啡依赖形成中的作用。方法;对吗啡依赖和戒断大鼠脑内NO含量和NOS活力进行测定。结果：未发现吗啡依赖和戒断大鼠脑内NO含量和NOS活力有改变。结论：对NO／NOS与吗啡依赖的关系还有待进一步研究。     

地塞米松脑内缓释对脑水肿和一氧化氮合酶的影响

目的探讨地塞米松(Dex)脑内缓释给药对实验性脑水肿和一氧化氮合酶(NOS)的影响。方法采用液氮冷冻雄性SD大鼠制备脑水肿模型,测量大剂量Dex脑内缓释给药、腹腔给药及不给药的各组脑组织含水量和NOS活性变化。结果Dex脑内缓释给药、腹腔注射和不给药组脑组织含水量分别为80.93%±2.27%、81.29%±2.22%和85.54%±2.69%,NOS活性则分别为(11.50±2.41)U/m l、(12.55±2.66)U/ml和(15.84±3.74)U/ml。两种给药方法之间无显著性差异,但与不给药组比较,均有显著性差异。结论Dex脑内缓释给药对脑水肿的疗效与大剂量腹腔注射类似,其机制可能与降低脑内NOS活性有关。     

二硫化碳对大鼠海马一氧化氮合酶活力和基因表达的影响

目的:探讨二硫化碳(CS2)对大鼠海马一氧化氮合酶(NOS)活力和基因表达的影响。方法:以吸入染毒法制作不同浓度CS2中毒大鼠模型:染毒2个月后,用Morris水迷宫法检测实验大鼠的学习记忆功能;以NOS测定试剂盒测定大鼠海马NOS活力;以半定量逆转录一聚合酶链式反应(RT-PCR)法测定神经元型一氧化氮合酶(nNOS)mRNA 含量的变化。结果:Morris水迷宫测试显示染毒后大鼠平均逃逸潜伏期较对照组延长,差异有显著性;各CS2染毒组大鼠海马NOS活性降低,与对照组比较差异有显著性,随CS2浓度的增加NOS活性降低,各染毒组间比较差异有显著性差异;染毒后海马nNOS mRNA含量比对照组显著减少,与CS2浓度呈剂量依赖关系,差异有显著性意义。结论:CS2致大鼠海马NOS活力降低及nNOS mRNA含量减少可能是CS2干扰学习记忆功能的机制之一。     

一氧化氮合酶在继发癫痫的脑膜瘤中表达及其生物学意义

目的探讨一氧化氮在脑膜瘤继发癫痫的发病机制中的作用。方法运用SABC免疫组化方法研究了一氧化氮合酶三种亚型在继发术前癫痫的脑膜瘤标本中的表达。结果在实验组与对照组脑膜瘤的组织切片中,诱生型一氧化氮合酶(iNOS)表达有非常显著性差异(P<0.01),神经元型一氧化氮合酶(nNOS)的表达有显著性差异(P<0.05),内皮组织型一氧化氮合酶(eNOS)的表达没有统计学意义(P>0.05)。结论一氧化氮参与了脑膜瘤继发的术前癫痫发作病理过程,iNOS是诱发脑膜瘤继发术前癫痫的内源性一氧化氮的主要合酶,nNOS可以增强iNOS的诱导作用。     

一氧化氮／一氧化氮合酶与神经创伤

一氧化氮是一种简单的气体分子,可在哺乳类神经细胞内经一氧化氮合酶作用产生。ＮＯ在神经创伤修复中的多重作用近年来已受到越来越多的重视。本文对ＮＯ／ＮＯＳ与神经创伤和再生之间的关系作一综述。     

一氧化氮合酶及其抑制剂与脑缺血

一氧化氮合酶(NOS)在脑缺血中具有双重作用,nNOS介导缺血早期神经元损伤,iNOS介导缺血晚期神经元损伤,eNOS则介导神经保护作用。对NOS抑制剂,尤其是选择性nNOS和iNOS抑制剂的研究,无疑将为缺血性脑损伤的治疗提供新途径。     

神经元型一氧化氮合酶在血管性痴呆大鼠海马中的表达

目的 探讨神经元型一氧化氮合酶(nNOS)在血管性痴呆(VD)大鼠海马中的表达。方法 将60只大鼠随机分为：对照组、VD12h组、VD1d组、VD3d组、VD7d组。采用反复夹闭双侧颈总动脉方法建立VD大鼠模型，用HE染色观察各组大鼠海马CA1区神经元的数目；应用免疫组化染色和Western印迹方法检测nNOS在大鼠海马中的表达。结果 VD12h组、VD1d组、VD3d组、VD7d组大鼠海马CA1区神经元数均明显下降。nNOS在对照组大鼠海马CA1区中弱表达．在VD12h组表达增强．VD1d组进一步增强，VD3d和7d组表达逐渐减弱。结论 nNOS可能参与缺血早期海马神经元的损害，是VD的发病机制之一。     

癫癎患者血清一氧化氮和一氧化氮合酶活性水平的研究

目的　探讨一氧化氮 (NK)和一氧化氮合酶 (NOS)在癫患者中血清活性水平及意义。方法　采用化学比色法对 10 0例癫患者血清中NO和NOS活性水平进行检测。结果　癫患者间歇期血清中NO和NOS活性水平显著高于对照组 (P <0 0 1)。结论　NO和NOS在癫病理过程中起重要作用。     

大鼠脑缺血再灌流后海马区一氧化氮合酶活性的变化

目的 :观察鼠全脑缺血再灌流后海马区NOS活性的变化。方法 :采用大鼠 4血管关闭方法制作全脑缺血再灌流模型。实验动物分为假手术组、缺血 10min组、再灌注 1、2、3d组 ,测定脑缺血再灌流后海马区NOS活性的变化。结果 :全脑缺血再灌注后海马组织NOS活性被激活上调。结论 :NO可能参与了海马CA1区迟发性神经元死亡 (DND)的发生。     

海藻氨酸致痫大鼠海马谷氨酸转运体功能的变化

目的研究腹腔注射海藻氨酸致癫痫发作后海马谷氨酸转运体功能的动态变化,以探讨谷氨酸转运体在癫痫发生中的作用机制。方法60只健康成年雄性Wistar大鼠,随机分为海藻氨酸组和对照组。海藻氨酸组30只大鼠均腹腔注射海藻氨酸10mg/kg,分别于注射后4h、24h、48h、5d和7d依据Racine制定的行为学标准观察大鼠的行为学改变。同时还分别测定不同时间点海马突触膜颗粒和海马组织切片对3氢-左旋-谷氨酸(3H-L-Glu)的摄取量,以反映谷氨酸转运体于点燃后不同时间点的活性。结果与对照组相比,海藻氨酸组大鼠海马突触膜颗粒谷氨酸转运体功能于点燃后4h减弱,对3氢-左旋-谷氨酸的摄取量减少(P<0.05),并持续至注射后第5～7天(P<0.01);海马组织切片检查显示谷氨酸转运体功能在点燃后4～48h增强,于注射后第5～7天减弱(P<0.05)。结论谷氨酸转运体功能的变化与海藻氨酸致痫大鼠模型癫痫的发生及易感性有关。     

Release of arginine, glutamate and glutamine in the hippocampus of freely moving rats: Involvement of nitric oxide

Using in vivo microdialysis, we have monitored the release of three amino acids (arginine, glutamate and glutamine) in the hippocampus of freely moving rats in response to various drugs. In response to N-methyl-d-aspartate (NMDA) infusion, extracellular glutamate was increased, glutamine was decreased and arginine remained unchanged. By contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) elicited an increase in arginine release but had no effect on either glutamate or glutamine. When S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was infused into the hippocampus, an increase in glutamate, a decrease in glutamine and no change in arginine were recorded. The effect of SNAP on extracellular glutamine levels was reversed by prior infusion of the guanylate cyclase inhibitor oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), however its effect on glutamate release was unchanged. Interestingly, SNAP was found to promote the release of arginine in the presence of ODQ. We also assessed the effect of two nitric oxide synthase inhibitors, N-nitro-l-arginine methylester (l-NAME) and 7-nitroindazole (7-NI), on the release of these amino acids. l-NAME was found to increase arginine and glutamate levels but decrease those of glutamine. In contrast, 7-NI reduced the release of all three amino acids. The results presented here confirm some but not all of the findings previously obtained using in vitro preparations. In addition, they suggest that complex relationships exist between the release of these amino acids, and that endogenous NO plays an important role in regulating their release.     

儿童癫癎患者血清一氧化氮及一氧化氮合酶活性水平的研究

目的　探讨一氧化氮 (NO)及一氧化氮合酶 (NOS)在儿童癫患者中血清活性水平及意义。方法　采用化学比色法对12 4例儿童癫患者血清中NO及NOS活性水平进行检测。结果　儿童癫患者发作期及间歇期血清中NO及NOS活性水平均显著高于对照组 (P <0 0 1) ,发作期血清中NO及NOS活性水平均高于间歇期 (P <0 0 5 )。结论　NO及NOS在儿童癫病理过程中起重要作用     

Vasodilatory actions of calcitonin gene-related peptide and nitric oxide in parenchymal microvessels of the rat hippocampus

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent dilators in a variety of vascular beds. Recent evidence suggests that NO may serve as an intermediary messenger for CGRP and/or CGRP may serve as an intermediary messenger for NO in the expression of vasodilation. The present study was designed to provide an initial characterization of the responses to NO and CGRP in parenchymal microvessels and to determine whether NO and/or CGRP act as intermediaries for one another. Microvessels in the parenchyma of in vitro hippocampal slices from rat brain were examined using computer-assisted videomicroscopy. The resting diameter of the microvessels ranged from 9 to 26 μm. Treatment with the nitric oxide synthase inhibitor, N^G-nitro-l-arginine ( -NNA; 100 μM) constricted vessels to 64.2% ± 3.0% of resting luminal diameter. Sodium nitroprusside (SNP; 1 μM), a donor of NO, reversed the -NNA-induced vasoconstriction by 77.0% ± 15.0%. CGRP alone (10 nM) elicited a small but significant vasodilatory effect on resting vascular tone (2.3% ± 0.6%). In the presence of -NNA, CGRP elicited a significant dose-dependent vasodilatory response, and 10 nM CGRP elicited a sizeable response, reversing the -NNA-induced constriction by 84.3% ± 15.5%. This CGRP-induced dilation was inhibited by pretreatment with the CGRP receptor antagonist, CGRP fragment (8–37) (1 μM). In contrast, pretreatment with 1 μM CGRP fragment (8–37) did not attenuate the SNP-induced dilation in the presence of -NNA. Taken together, these findings demonstrate that CGRP and NO are potent dilators of parenchymal microvessels, and that NO provides a substantial relaxant effect on resting tone. In addition, the results indicate that CGRP is not a necessary intermediary in NO-induced dilation, and that NO is not a necessary intermediary in CGRP-induced dilation in parenchymal microvessels.     

Methylene blue inhibits hippocampal nitric oxide synthase activity in vivo

The aim of the present study was to investigate the effect of methylene blue, a guanylate cyclase inhibitor, on the hippocampal nitric oxide synthase activity in vivo. We used a microdialysis-based technique of measuring conversion of [3H]l-arginine to [3H]l-citrulline in freely moving rats. The administration of methylene blue (0.1 and 1 mM) via the microdialysis probe caused a dose-dependent decrease in [3H]l-citrulline efflux comparable with the effect of unselective NOS inhibitor NG-nitro-L-arginine (2 mM). We conclude that methylene blue inhibits brain NOS activity in vivo and thus interferes with NO-cGMP cascade in different levels.     

一氧化氮合酶、谷氨酸在局灶脑缺血中的变化

目的　观察一氧化氮合酶 (NOS)和谷氨酸 (Glu)在脑缺血时的改变。方法　应用大鼠大脑中动脉闭塞局灶脑缺血模型 ,观察脑缺血 1h后NOS和Glu含量的变化。结果　缺血 1h后NOS活性显著升高(P <0 .0 5 )、Glu含量亦显著升高 (P <0 .0 1) ;用L NMMA处理后 ,NOS活性显著降低 (P <0 .0 1) ,Glu含量亦降低 (P <0 .0 5 )。结论　Glu生成过多可激活NOS ;抑制NOS活性可减少Glu的生成。