一氧化氮在颅脑损伤手术麻醉期间含量变化及异丙酚的保护作用

目的 探讨急性颅脑损伤（ACI） 患者围术血浆一氧化氮（NO）、一氧化氮合成酶（NOS）、氧自由基（OFR）、脂质过氧化物（LPO）、内皮素（ET）、降钙素基因相关肽（CGRP）含量变化及新型静脉麻醉剂异丙酚（Pro）对其影响。方法 ACI患者40例,根据麻醉方法不同随机分为观察组（异丙酚组）和对照组（α-羟基丁酸钠组）。观察麻醉诱导前、开颅手术去骨瓣后1、3、6、12、24hNOS/NO(分别用T0－T5表示）;麻醉诱导前、开颅手术后1、3hOFR/LPO`ET/CGRP的水平变化。结果 研究发现术前患者血中NO、NOS均高 于正常对照组,其中NOS显著增高;血中OFR、LPO、ET显著高于正常对照组。与对照组相比异丙酚组NO、NOS自妈至经科（T0－T5）呈降低趋势。NOS于开颅手术后1h(T1)达到正常水平,NO于T2时也达到正常水平。FOR、LPO、ET呈显著降低趋势且于T2时达到正常水平。CGRP呈持续升高。结论 ACI患者术前就存在OFR代谢紊乱及NO／NOS、ET／CGRP间含量失衡,开颅手术可导致继发性脑缺血再灌注损害。临床麻醉剂量的Pro具有非选择性NOS抑制剂、OFR清除剂、ET拮抗剂特性,并能提高CGRP水平,具有多途径、多位点脑保护剂特性。     

异丙酚对急性颅脑损伤患者血内一氧化氮及相关因子含量的影响

目的 观察异丙酚（PRO）对急性颅脑损伤（ACI）患者围术期血内一氧化氮（NO）产量、一氧化氮合成酶（NOS）、红细胞超氧化物歧化酶（SOD）活性、氧自由基（OFR）含量的影响。方法 40例ACI患者随机分为PRO组和γ－OH组。观察自麻醉诱导前至开颅手术去骨瓣后1，3，6，12，24h(T0-T5)诸指标水平变化。并以40例健康者作术前对照。结果 与正常对照组相比，两组术前NOS、OFR均显著增高（P＜0．05，P＜0．01），SOD显著降低（P＜0．01）。与γ－OH组相比，PRO组NO、NOS自始至终呈降低趋势，NOS于T1、SOD于T2、NO及OFR于T3时达到正常水平（与T0相比均P＜0．01）。结论 临床麻醉剂量的PRO具有非选择性NOS抑制剂、OFR清除剂特性，对ACI患者有多位点的脑保护作用。     

纳洛酮对急性颅脑损伤患者血浆内皮素、降钙素基因相关肽和氧自由基含量的影响

目的　探讨纳洛酮对急性颅脑损伤(ACI)患者开颅手术后血浆内皮素(ET)、降钙素基因相关肽(CGRP)和氧自由基(OFR)含量的影响。方法　以放射免疫分析方法测定40例ACI患者手术前后血浆ET、CGRP含量,用电子自旋共振(ESR)方法测定血浆OFR浓度,并以40例健康献血者为术前对照。结果　ACI患者术前血浆ET、OFR明显高于正常对照组(均P＜0.01);开颅手术后120min两组ET、OFR较术前有显著性升高(均P＜0.01),CGRP显著性降低(P＜0.05)。A组给予纳洛酮20μg/kg静脉注射后30min,血浆ET、OFR均较治疗前显著性降低(均P＜0.01),而CGRP较治疗前呈显著性升高(P＜0.01),与B组组间比较有显著性差异(均P＜0.01)。结论　临床治疗剂量的纳洛酮可明显提高ACI患者体内CGRP水平,降低ET,清除OFR而具有脑保护作用。     

慢性乙型肝炎患者血浆内皮素、一氧化氮、心钠素、降钙素基因相关肽的变化及意义

目的　探讨慢性乙型肝炎、肝炎肝硬化患者血浆内皮素 (ET)、一氧化氮 (NO)、心钠素 (ANP)、降钙素基因相关肽 (CGRP)的变化及相互关系。方法　对 60例慢性乙型肝炎、3 0例肝炎肝硬化患者 ,采用放射免疫法测定治疗前后ET、ANP、CGRP ,硝酸还原酶法测定NO并作相关分析 ,肝硬化患者同时测定门静脉内径及血流量。结果　①慢性乙型肝炎、肝硬化患者血浆ET、NO明显高于正常对照组 ,均P <0 .0 5 ,且随着病变的加重 ,两者升高得更显著 ,CGRP水平明显低于正常对照组 ,P <0 .0 1;ANP与对照组无差别 ,P >0 .0 5。②慢性乙肝组肝功能好转 ,ET、ANP、CGRP无显著性变化 ,P >0 .0 5 ,肝硬化组肝功能好转 ,ET下降 ,P <0 .0 1,CGRP上升 ,P <0 .0 5。慢乙肝重度、肝硬化组治疗后NO下降 ,P <0 .0 5 ,P <0 .0 1。③直线相关分析表明 ,ET与NO呈正相关 ,P <0 .0 1;ET、NO、ANP、CGRP与肝功能无密切关系。结论　血管活性因子ET、NO、ANP、CGRP共同参与了慢性乙型肝炎的发生发展过程     

血管内皮细胞钙粘蛋白在2型糖尿病患者中的变化及意义

目的 探讨2型糖尿病(T2DM)患者血管内皮细胞钙粘蛋白(VEC)以及内皮素(ET)、一氧化氮(NO)、一氧化氮合酶(NOS)等的变化及其意义.方法 对T2DM患者85例和健康人80例,测定VEC、ET、NO、NOS水平及血糖等,分析VEC等变化及其意义.结果 T2DM组糖化血红蛋白( HbA1c )、空腹血糖(FBG)、VEC、ET明显高于健康人组;VEC与HbA1c 、EF呈正相关,NO与NOS呈正相关.结论 血管内皮功能障碍可能是导致血管病变的原因,VEC、ET、NO、NOS可能参与T2DM患者血管病变的发生和发展,可作为T2DM大血管并发症发生的预测和检测指标.     

急性脑血管病患者血浆一氧化氮和内皮素含量测定

通过观测正常人和急性脑血管病患者的血浆一氧化氮 (NO)和内皮素 (ET)水平 ,探求NO和ET在急性脑血管病发作过程中的病理生理意义。方法　用Green’s法测定血浆NO ,用放射免疫法测定血浆ET。结果　正常对照组 (A组 ) 2 4例 ,平均血浆NO 2 6 5 2± 2 5 1μmol/L ,ET 45 81± 11 2 1ng/L ;脑出血组 (B组 ) 2 7例 ,平均血浆NO 18 12± 4 14μmol/L ,ET132 41± 2 1 0 5ng/L ;脑梗死组 (C组 ) 4 2例 ,平均血浆NO 18 0 0± 3 12 μmol/L ,ET 12 9± 9 37ng/L。与A组相比较 ,B组和C组均有NO显著降低 (P <0 0 5 ) ,ET显著升高 (P <0 0 1) ;B组与C组之间无显著差异 (P >0 0 5 )。结论　在急性脑血管病发作过程中 ,血浆NO和ET的含量变化 ,可能促进了疾病的发生和发展     

醒脑静注射液对实验性脑缺血-再灌注损伤中一氧化氮和内皮素水平的影响

目的 :探讨醒脑静注射液 (XNJI)对脑缺血再灌注损伤 (CIRI)家兔一氧化氮 (NO)和内皮素 (ET)水平的影响。方法 :采用“四动脉闭塞法”制备家兔 CIRI模型 ,随机分为假手术对照组 (A组 )、脑缺血再灌注组(B组 )和脑缺血再灌注加 XNJI治疗组 (C组 )。分别在脑缺血前、缺血 30分钟及再灌注 30、6 0和 12 0分钟不同时间点 ,检测血浆及脑组织 NO浓度和 ET含量。结果 :脑缺血再灌注期间 ,血浆和脑组织 NO水平明显下降 ,血浆为 (43.80± 10 .4 0 )μmol/ L、(43.6 0± 8.96 )μm ol/ L、(37.5 0± 13.6 0 )μmol/ L、(39.80± 8.2 2 )μmol/ L、(40 .70± 7.86 )μmol/ L (P<0 .0 5和 P<0 .0 1) ,脑组织为 (319.0 0± 70 .70 )μmol/ g(P>0 .0 5 ) ;ET水平显著升高 ,血浆为 (73.80± 34.70 ) ng/ L、(81.30± 32 .5 0 ) ng/ L、(78.2 0± 36 .80 ) ng/ L、(10 4 .0 0± 4 2 .0 0 ) ng/ L、(111.0 0± 5 0 .70 ) ng/ L(P<0 .0 5和 P<0 .0 1) ,脑组织为 (93.10± 4 2 .30 ) ng/ g(P<0 .0 5 ) ;使用 XNJI后 ,上述各指标的异常变化明显减轻 ,与对照组相比有显著性差异 (P<0 .0 5和 P<0 .0 1)。结论 :XNJI可提高机体 NO水平、降低 ET水平而抗 CIRI     

失血性休克复苏时心肌损伤和一氧化氮的变化及灵芝多糖的干预作用

目的 :探讨失血性休克和复苏再灌注过程中心肌损伤和一氧化氮 (NO)浓度的变化及灵芝多糖的干预作用。方法 :复制家兔失血性休克再灌注模型 ,随机分成假手术组、生理盐水再灌注组和质量分数为 1%的灵芝多糖再灌注组 ;观察 3组动物平均动脉血压 (MAP)、心功能、血浆 NO浓度及心肌 NO含量和一氧化氮合酶(NOS)活性的变化。结果 :两个再灌注组动物在失血性休克 4 0 m in时左心室舒张末压 (L VEDP)比休克前及假手术组略有升高 ,但差异不显著 (P均 >0 .0 5 ) ,左心室内压最大变化速率 (± dp/dt max)则明显降低 (P均 <0 .0 5 ) ,血浆 NO浓度则显著升高 (P均 <0 .0 5 )。生理盐水再灌注组动物再灌注 4 0 min时 ,心功能较休克 4 0 m in时进一步降低 (P<0 .0 5 ) ,血浆 NO浓度进一步升高 ,心肌 NOS活性和 NO含量明显高于假手术组 (P均 <0 .0 5 )。灵芝多糖组再灌注 4 0 min时较生理盐水再灌注组、心功能明显改善 ,血浆 NO浓度、心肌 NO含量和心肌 NOS活性均明显降低 (P均 <0 .0 5 )。结论 :失血性休克再灌注过程中心肌 NOS活性、血浆 NO浓度、心肌NO含量均升高 ,而心功能降低 ,提示 NO在失血性休克再灌注心肌损伤中起重要作用 ;而灵芝多糖可通过抑制 NOS活性、降低 NO浓度对失血性休克再灌注心肌损伤起保护作用。     

通心络对肺心病急性加重期患者血浆内皮素一氧化氮降钙素基因相关肽的影响

目的:探讨通心络胶囊对肺心病急性加重期患者血浆ET、NO和CGRP的影响。方法:将住院肺心病急性加重期患者随机分成常规组、联用组,治疗前后抽血检测NO、CGRP及ET,并与健康组比较。结果:肺心病急性加重期患者血浆NO和CGRP显著低于健康人(P<0.01),ET显著高于健康人(P<0.01);2组治疗前后NO、CGRP和ET均明显改善(P<0.05或P<0.01),联用组与常规组治疗后比较差异有显著性(P<0.05)。结论:通心络胶囊治疗肺心病的临床疗效可能为减少ET,升高NO和CGRP。     

同种异体肾移植时血流动力学变化及一氧化氮在其中的作用

目的　观察肾移植时全身和肾脏血流动力学变化 ,并评价NO在其中的作用。方法　随机选取肾移植手术患者 2 8例 ,分为高血压组 (H组 ,n =14 )和血压正常组 (N组 ,n =14 )。麻醉前、开放前及开放后 5min、30min、1h记录血流动力学指标 ,开放后 5、30min时测量移植肾RBF ;静脉血测定NO、NOS和ET血浆浓度。另抽测 14例无肾脏疾患志愿者血样 ,作为NO、NOS和ET水平的对照值。结果　两组肾移植患者血流动力学变化趋势相近。两组肾移植患者麻醉前NO、NOS及ET均明显高于对照组 (P <0 0 5 ) ,而两组间及组内各时点均没有显著性差异 (P >0 0 5 ) ;对照组和肾移植组中 ,NO、ET与MAP之间分别呈负、正相关 (P <0 0 5 ) ;但肾移植组NO、ET与移植肾RBF相关不明显 (P >0 0 5 )。结论　肾移植时血压正常和偏高时血流动力学相差不大 ;NO -ET只是其调控因素之一     

精神分裂症患者一氧化氮合酶活性与发病机制相关性

目的通过测定首发精神分裂症患者和正常人的血清一氧化氮合酶(NOS)活性，比较和分析他们之间的差异，探讨NOS活性以及一氧化氮(NO)能神经系统的功能变化与精神分裂症的关系。方法采用比色法分别测定首发未用抗精神病药的精神分裂症患者(研究组)、临床症状缓解的精神分裂症患者(缓解组)和正常对照者的血清NOS活性。结果研究组的血清NOS活性为6.3665±1.2260(n=39)，明显高于症状缓解组(4.1204±0.9908，n=27，P<0.01)和正常对照组(3.2660±1.0320，n=27，P<0.01)；症状缓解组的NOS活性也明显高于正常对照组(P<0.01)。结论精神分裂症患者血清NOS活性明显增高，L-精氨酸-NO神经通路功能的紊乱可能是精神分裂症的发病机制之一，也可能成为一个新的治疗靶系统。     

Nitric oxide: therapeutic opportunities

Fifteen years after the discovery of nitric oxide as a biological mediator how close are new therapies? This article describes the roles of nitric oxide, illustrates how its discovery is altering the way in which certain established drugs are being used and reviews new therapeutic developments.     

Nitric Oxide-based Possibilities for Pharmacotherapy

The goal of nitric oxide (NO) based pharmacotherapy is to reach proper homeostasis of NO metabolism in the target tissue where endogenous production of NO is either too weak or excessively increased. In addition to the classic NO-based therapy of cardiovascular conditions with nitrates, a variety of new therapeutic possibilities have emerged including sexual disorders, gastrointestinal system, immunology, tumour growth regulation and respiratory disorders. NO levels of target tissues can be affected directly by NO donors, or indirectly by increasing the level of L-arginine, a substrate of nitric oxide synthase (NOS). While increased production of NO by induceable NOS (iNOS) by, for example, cytokines does not at present seem therapeutically meaningful, increased NO production by constitutive NOS (cNOS) may be involved in the beneficial effects of ACE inhibitors or oestrogens. NO production may be pharmacologically decreased by inhibition of expression of iNOS by glucocorticoids while both cNOS and iNOS derived NO production is inhibited by administration of false substrates, for example L-NAME. Additionally, the respiratory system and related vessels can be reached directly and more selectively by inhalation of pure NO gas. Possible problems in administering NO and perhaps some NO-donors include the toxic nature of the compound itself whereby vital enzyme systems may be inhibited and tissue damaging radicals formed. Future prospects of NO-based pharmocotherapy may feature selective ligands to different NOS isoforms and tissue selective donors that release NO in a controlled fashion.     

雾化吸入氯胺酮对哮喘大鼠肺组织一氧化氮及一氧化氮合酶的影响

目的通过建立大鼠支气管哮喘模型,观察不同浓度氯胺酮对哮喘大鼠肺组织iNOS活性及NO含量的影响。方法SD大鼠随机分成对照组(N组)、哮喘模型组(A组)、不同浓度氯胺酮预处理组(分别为K1组、K2组)和地塞米松组(D组),每组8只。A组大鼠用卵白蛋白辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发哮喘;氯胺酮处理组大鼠用同样方法致敏,但在激发前分别给予雾化吸入氯胺酮25 g/L(K1组)和50 g/L(K2组);D组在激发前给予雾化吸入0.01%地塞米松;N组用生理盐水替代卵蛋白进行注射和吸入。每组分别测定其肺组织NO2-/NO3-水平、肺组织诱导型NOS(iNOS)和原生型NOS(cNOS)活性水平,并用免疫组织化学法观察iNOS在大鼠哮喘模型肺组织中的分布。结果A组肺组织中NO2-/NO3-和iNOS水平升高,iNOS和肺组织NO2-/NO3-水平呈高度正相关;K1、K2组肺组织中NO2-/NO3-和iNOS水平低于A组(P<0.05);D组肺组织中NO2-/NO3-和iNOS水平亦低于A组(P<0.05)。结论25 g/L或50 g/L的氯胺酮雾化吸入可抑制哮喘大鼠肺组织iNOS活性,降低NO含量,减轻大鼠肺部炎症。     

Nitric oxide in the human uterine cervix: Endogenous ripening factor

The human uterine cervix can produce nitric oxide (NO), a free radical with an ultra‐short half‐life. The release of NO changes during pregnancy and is increased in early nonviable pregnancies compared to normal uncomplicated pregnancies. This review concentrates on the role of NO release in cervical ripening in pregnant women. Also some suggestions on future aspects are discussed.     

Low‐intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis

Summary. Low‐intensity ultrasound (US) increases tissue perfusion in ischemic muscle through a nitric oxide (NO)‐dependent mechanism. We have developed a model to expose endothelial cells to well‐characterized acoustic fields in vitro and investigate the physical and biological mechanisms involved. Human umbilical vein endothelial cells (HUVEC) or bovine aortic endothelial cells (BAEC) were grown in tissue culture plates suspended in a temperature‐controlled water bath and exposed to US. Exposure to 27 kHz continuous wave US at 0.25 W cm^?2 for 10 min increased HUVEC media NO by 102 ± 19% (P < 0.05) and BAEC by 117 ± 23% (P < 0.01). Endothelial cell NO synthase activity increased by 27 ± 24% in HUVEC and by 32 ± 16% in BAEC (P < 0.05 for each). The cell response was rapid with a significant increase in NO synthesis by 10 s and a maximum increase after exposure for 1 min. By 30 min post‐exposure NO synthesis declined to baseline, indicating that the response was transient. Unexpectedly, pulsing at a 10% duty cycle resulted in a 46% increase in NO synthesis over the response seen with continuous wave US, resulting in an increase of 147 ± 18%. Cells responded to very low intensity US, with a significant increase at 0.075 W cm^?2 (P < 0.01) and a maximum response at 0.125 W cm^?2. US caused minor reversible changes in cell morphology but did not alter proliferative capacity, indicating absence of injury. We conclude that exposure of endothelial cells to low‐intensity, low‐frequency US increases NO synthase activity and NO production, which could be used to induce vasodilatation experimentally or therapeutically.     

大鼠创伤性脑水肿一氧化氮及其合成酶的变化

目的：探讨脑损伤后一氧化氮（ＮＯ）及一氧化氮合酶（ＮＯＳ）与脑水肿的关系。方法：建立大鼠创伤性脑水肿模型,按不同时间点处死动物,测定其脑含水量及静脉血ＮＯ 和脑组织中ＮＯＳ。结果：脑创伤后脑含水量随静脉血ＮＯ的增加而增加,组织ＮＯＳ则随ＮＯ 的增加而下降。结论：创伤性脑水肿与血ＮＯ 有密切相关性,组织中ＮＯＳ则是该过程的可能催化剂     

Nitric oxide and the control of renin secretion

Summary— Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, renal, immune and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, pituitary and other endocrine glands, and evidence is accumulating that it contributes to the regulation of the secretion of renin by the kidneys. The enzyme nitric oxide synthetase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa , a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney and is responsive to changes in nitric oxide levels. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro , suggesting a stimulatory role for the L-arginine-nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa and beta adrenoceptor mechanisms that regulate renin secretion. Future research should clarify the mechanisms by which nitric oxide regulates the secretion of renin and establish the physiological significance of this regulation.     

一氧化氮合酶抑制剂对严重烧伤大鼠的作用研究

目的 :研究一氧化氮合酶 (NOS)抑制剂对严重烧伤大鼠体内一氧化氮 (NO)含量及 NOS表达的影响及其与预后的关系。方法 :复制大鼠重症烧伤模型 ,检测应用非选择性 NOS抑制剂 N 硝基 L 精氨酸甲酯(L NAME)和选择性诱生型 NOS(i NOS)抑制剂氨基胍 (AG)后大鼠血液中 NO代谢产物 (NO- 2 /NO- 3 )以及肺和十二指肠组织中神经型 NOS(n NOS) m RNA的表达水平 ,同时统计各组大鼠的存活率。结果 :烧伤后大鼠血液中 NO- 2 /NO- 3 含量明显增高 ,L NAME和 AG都能抑制 NO2 /NO- 3 的升高 ,L NAME作用更为明显 ;烧伤后 n NOS的 m RNA表达在肺和十二指肠中均有不同程度升高 ,AG和 L NAME使 n NOS表达增加 ,AG作用更为明显 ;L NAME组动物存活时间较对照组显著缩短 ,AG组动物存活时间明显延长。结论 :结构型NOS(c NOS)与 i NOS在烧伤休克病理生理过程中的作用明显不同 ,i NOS活性过度增高与烧伤休克发病关系密切     

N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets

BACKGROUND: N-acetyl-L-cysteine, a thiol compound, has been shown to potentiate the inhibition of platelet aggregation exerted by organic nitrates and to increase the anti-aggregating effect of L-arginine, which promotes endogenous synthesis of nitric oxide (NO) acting as substrate of platelet constitutive nitric oxide synthase (NOS). It is not known whether this thiol can exert direct effects on platelet aggregability. MATERIALS AND METHODS: 14 healthy male volunteers provided platelet samples to investigate whether N-acetyl-L-cysteine directly influences platelet function and intraplatelet levels of 3',5' cyclic guanosine monophosphate (cGMP), which represents the second messenger involved in NO-induced antiaggregation. Some experiments were repeated in the presence of NOS inhibitor NG-monomethyl-L-arginine (L-NMMA), of nitric oxide-sensitive guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), of the selective cGMP phosphodiesterase inhibitor zaprinast and of calcium ionophores (A23187, ionomycin). RESULTS: N-acetyl-L-cysteine at 3000-6000 micromol L-1 decreases the responses of human platelets both in platelet-rich plasma (aggregation induced by adenosine 5-diphosphate) and in whole blood (aggregation induced by collagen). The anti-aggregating effect was prevented by preincubation with L-NMMA and guanylyl cyclase inhibitor ODQ. In resting platelets, N-acetyl-L-cysteine increased the levels of cGMP starting from a concentration of 3000 micromol L-1. Permeabilized platelets exhibited an increased sensitivity to the anti-aggregating effect of N-acetyl-L-cysteine. Also, cGMP phosphodiesterase inhibition or the increase in calcium availability, enhanced N-acetyl-L-cysteine effects on platelets. CONCLUSION: N-acetyl-L-cysteine exerts direct anti-aggregating effects through an increased bioavailability of platelet nitric oxide.