川芎嗪对发育期大鼠惊厥性脑损伤海马ATP酶与脑含水量变化的影响

目的观察发育期大鼠反复惊厥后海马ATP酶与脑含水量的动态变化及川芎嗪干预对其的影响。方法162只20日龄健康sD大鼠随机分为3组：对照组、惊厥组及川芎嗪干预组。通过三氟乙醚反复吸入（连续6次，每天1次）制作发育期大鼠惊厥动物模型。取海马组织匀浆，检测各组动物反复惊厥后6h、1d、3d、7d海马组织中Na^＋-K^＋-ATP酶、Ca2^＋-ATP酶的活性变化，同时观察脑含水量变化和光镜下海马区神经元病理改变。结果反复惊厥后6h、1d、3d海马Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性均较对照组显著降低（P＜0．01），伴随脑含水量显著升高（P＜0．01），第7天三者与对照组相比较差异均无统计学意义（P＞0、05）。脑含水量变化与海马Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性变化均呈显著负相关（前者r=-0．711，后者r=-0．673，P均＜0．01）。川芎嗪干预组海马神经元水肿、变性坏死明显减轻，各时间点Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性较惊厥组显著升高（P＜0．05或P＜0、01），脑含水量显著降低（P＜0．01）。结论Na^＋K^＋ATP酶、Ca^2＋-ATP酶的活性降低与惊厥性脑水肿和海马神经元迟发性损害密切相关，川芎嗪对发育期惊厥性脑损伤的保护作用可能与提高海马Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性有关。     

川芎嗪对发育期大鼠惊厥性脑损伤后海马caspase-1 mRNA表达的影响

目的:探讨发育期大鼠反复惊厥后海马caspase 1 mRNA表达及川芎嗪对其表达的影响。方法:162只20日龄健康SD大鼠随机分为对照组、惊厥组及川芎嗪组。采用三氟乙醚反复吸入(连续6次,每日1次)方法制作发育期大鼠惊厥模型。逆转录聚合酶链反应(RT PCR)检测各组动物反复惊厥后6 h及1、3、7 d时海马组织caspase 1 mRNA的表达,同时观察脑含水量的变化和光镜下海马区神经元病理改变,并对脑损伤进行病理半定量积分。结果:川芎嗪干预组各时间点caspase 1 mRNA表达较惊厥组均显著下调,脑含水量(7 d时除外)和脑损伤积分显著降低(P均<0.01),海马神经元水肿、变性、坏死均明显减轻。结论:川芎嗪能有效减轻惊厥性脑水肿和海马神经元病理损伤,其机制可能与抑制海马caspase 1 mRNA异常表达有关。     

反复惊厥幼鼠脑内氧化抗氧化水平和神经元凋亡

目的探讨反复惊厥后幼鼠脑内氧化、抗氧化能力平衡的变化和神经元凋亡的关系。方法96只20日龄健康SD大鼠随机分为两组:对照组及惊厥组。通过三氟乙醚反复吸入(连续6次,每天1次)制作发育期大鼠惊厥动物模型。检测各组动物反复惊厥后6h、1d、3d、7d海马组织MDA含量、SOD活性、T-AOC水平变化,同时原位末端标记法(TUNEL)进行大鼠海马神经元凋亡检测。结果反复惊厥后6h、1d、3d海马MDA含量均较对照组显著增高,SOD活性及T-AOC水平显著降低(P<0.01),皆以第1天改变最显著,第7天三者与对照组相比较差异均无统计学意义(P>0.05);而海马神经元凋亡却于反复惊厥后1d才显著增加,持续到惊厥后7d仍显著多于对照组(P<0.01)。结论反复惊厥后海马MDA含量显著增高,SOD活性、T-AOC水平显著降低,且三者的变化皆发生在神经元凋亡增多之前,提示氧化损伤、抗氧化能力下降可能参与惊厥大鼠海马神经元凋亡的发生。     

铅对大鼠海马和大脑皮质NOS活性的影响

目的 观察实验性铅中毒对大鼠海马和大脑皮质一氧化氮合酶（NOS）性的影响，探讨NOS在铅中毒中枢系统损害中的作用机制。方法 4周龄Wistar雄性大鼠按45mg/kg剂量行醋酸铅灌胃30d；大鼠海马和大脑皮质总NOS和诱导型一氧化氮合酶（iNOS）活性测定采用NOS催化L-Arg和氧分子生成NO法。结果 与空白对照纽大鼠比较，染铅组大鼠海马和大脑皮质总NOS活性明显降低，而iNOS活性均升高，差异有显著性（P〈0．01）。结论 铅可以使大鼠海马和大脑皮质总NOS活性降低，iNOS活性升高。     

地黄苏合香合剂对早期肝性脑病大鼠一氧化氮、一氧化氮合酶、肿瘤坏死因子-α的影响

目的观察中药地黄、苏合香(地苏合剂)对CCl4致早期肝性脑病(HE)大鼠模型的治疗作用。方法采用灌胃给予CCl4致化学性肝损伤大鼠模型,检测大鼠血清一氧化氮(NO)含量、一氧化氮合酶(NOS)活性及大鼠海马肿瘤坏死因子-α(TNF-α)水平。结果模型组大鼠血清NO含量、NOS活性以及海马TNF-α水平较对照组明显升高(P<0.01);服用地苏合剂12周后高剂量治疗组模型鼠血清NO含量、总NOS活性以及海马TNF-α水平较模型组均明显降低(P<0.01)。结论地苏合剂可以通过降低早期HE大鼠血清NO含量、总NOS活性以及海马TNF-α水平延缓HE的发生、发展。     

鞘内注射GDNF对神经病理性疼痛大鼠脊髓NO含量和NOS活性的影响

目的:探讨鞘内注射胶质细胞源性神经营养因子(GDNF)对脊神经结扎(SNL)大鼠脊髓组织中一氧化氮(NO)含量和一氧化氮合酶(NOS)活性的影响.方法:采用大鼠L5～L6脊神经结扎模型,将SD雄性大鼠随机分为对照组,假手术组,单纯SNL组(SNL后蛛网膜下腔注射生理盐水)和GDNF治疗组(SNL后蛛网膜下腔注射GDNF).每组根据处死动物的时间不同又分为术后3d组、术后7d组和术后14d组3个亚组,每组各10只.于大鼠脊神经结扎后不同时间点(3d、7d和14d)进行行为学评估后断头处死大鼠,取其脊髓组织测定NO含量和NOS活性.结果:与对照组和假手术组比较,SNL组脊髓组织中NO含量和NOS活性在术后3d开始明显增高,一直持续到术后14d(P<0.01或0.05);与SNL组比较,GDNF组脊髓组织中NO含量和NOS活性明显降低且持续至术后14d(P<0.01或0.05).结论:大鼠脊髓组织中NO和NOS可能参与了SNL所致病理性疼痛的发生,鞘内注射GDNF减轻神经病理性疼痛的发生可能与降低脊髓组织NO含量和NOS活性有关.     

肠系膜淋巴管结扎对失血性休克大鼠肺组织一氧化氮及其表达的影响

目的 观察结扎肠系膜淋巴管对不同时期重症失血性休克大鼠肺组织一氧化氮（NO）及其表达的影响，探讨肠淋巴途径在休克大鼠急性肺损伤（ALI）中的作用。方法 雄性Wistar大鼠78只，按随机数字表法分为假手术组（n=6）、休克组（n=42）和结扎组（n=30）。休克组与结扎组复制重症失血性休克模型，结扎组于休克复苏后行肠系膜淋巴管结扎术；休克组于休克后90min、输液复苏后0h，休克组及结扎组于输液复苏后1、3、6、12和24h各时间点处死大鼠，制备肺组织匀浆，检测NO及其合酶的变化；用逆转录-聚合酶链反应（RT—PCR）测定各组大鼠肺组织诱生型一氧化氮合酶（iNOS）．mRNA表达。结果 休克组大鼠复苏后3h肺组织NO含量、NOS活性及iNOSmRNA表达开始升高，复苏后6～12h持续在较高水平，均显著高于假手术组、休克后90min及复苏后0h（P〈0．05或P〈0．01）；结扎组仅于3h和6h增高，且结扎组复苏后6、12和24h肺组织NO含量、NOS活性以及iNOSmRNA表达均显著低于休克组相同时间点（P〈0．05或P〈0．01）。结论 肠系膜淋巴管结扎可降低重症失血性休克大鼠肺组织NO生成及iNOSmRNA表达，从而减轻肺损伤。     

大黄素对鼠脑爆震伤一氧化氮和一氧化氮合酶的影响

目的:观察鼠颅脑爆震伤后脑组织中一氧化氮(NO)浓度和一氧化氮合酶(NOS)活性的变化及大黄素对伤后NO浓度和NOS活性的影响.方法:模拟鼠颅脑爆炸伤模型,大黄素组腹腔注射大黄素(10 mg/kg),伤后2、4、12、24 h测定脑组织NO浓度和NOS活性.结果:伤后各组动物脑组织NO含量和NOS活性均显著升高,与正常对照组差异显著;大黄素组各时相NO含量和NOS活性均明显低于模型组;大黄素组NO含量和NOS活性动态变化呈显著正相关.结论:大黄素可降低颅脑爆炸伤大鼠脑组织中NO浓度和NOS活性,对大鼠颅脑爆炸伤有保护作用.     

肢体反复短暂缺血再灌注后脑组织一氧化氮的动态变化

目的：观察大鼠短暂肢体缺血再灌注后脑组织一氧化氮含量动态变化，探讨一氧化氮在肢体缺血预处理脑保护中的作用。方法：实验于2003-08／2004-09在新乡医学院生理教研室和河北医科大学病理生理研究室完成。选择健康雄性Wistar大鼠72只，随机分成假手术组，短暂肢体缺血再灌注(limb ischem&;#237;a reperfusion，LIR)组和NG-硝基-L-精氨酸甲酯(L-NAME)+LIR组，观察LIR后不同时间点血清和海马CA1区脑组织中一氧化氮含量和一氧化氮合酶(nitric oxide synthase，NOS)活性的变化。结果：LIR后即刻血清一氧化氮生成明显增加，达到高峰，与假手术组比较升高显著(P&;lt;0．01)。6h降低，48h又有一定程度的回升。而LIR后即刻海马CA1区组织一氧化氮生成开始升高，6h达到高峰，24h降至接近假手术组水平，48h又有明显的升高。LIR后血清和海马CA1区NOS活性的变化规律与一氧化氮生成相似。结论：肢体反复短暂缺血再灌注后脑组织一氧化氮这种动态变化可能发挥对脑的保护作用。     

葛根素对血管性痴呆大鼠脑组织NO、NOS含量及病理学的影响

目的:探讨葛根素对血管性痴呆(VD)大鼠脑组织一氧化氮(NO)、一氧化氮合酶(NOS)浓度及病理学改变的影响。方法:中动脉阻塞法制备VD动物模型,检测脑组织NO、NOS含量,HE染色、尼氏染色检测病理变化。结果:模型组较空白组海马及大脑皮质NO、NOS含量显著升高,神经元丢失及胶质细胞增生;葛根素组较模型组海马及大脑皮质NO、NOS含量显著降低,神经元损伤得以恢复。结论:葛根素对血管性痴呆有一定防治作用。     

抑郁症患者血清一氧化氮及一氧化氮合成酶的检测及其临床研究

目的 探讨血清NO、一氧化氮合成酶(NOS)活力与抑郁症的关系.方法 纳入136例符合中国精神障碍分类与诊断标准的抑郁症患者(实验组)和120名健康志愿者(对照组),进行血清NO水平及NOS活力的检测,并进行对照分析.结果 实验组血清NO水平(70.05±10.34)μmol/L及NOS活力平均水平(29.49±5.12)U/L均高于正常对照组[(67.17±16.52)μmol/L、(26.99±2.87)U/L],差异均有统计学意义(P均<0.05);抑郁症患者中服药组血清NO水平(74.42±8.80)μmol/L及NOS活力平均水平(27.71±5.46)U/L均低于未服药组[(78.81±12.28)μmoL/L、(30.49±4.65)U/L],两者相比,差异有统计学意义(P均<0.05).结论 抑郁症患者血清NO水平及NOS活力升高,NO升高可能是抑郁症发病的影响因素;抗抑郁药可能通过降低血清NO水平而起到抗抑郁作用.     

Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients were studied both before, during an asymptomatic phase (t ₀), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide donor able to induce an experimental migraine attack (t ₁). The nitric oxide levels were analyzed as nitrite accumulation in serum samples, in peripheral blood mononuclear cell extracts, and culture supernatants. Basal nitrite levels in serum samples and peripheral blood mononuclear cell culture supernatants of migraine patients and healthy subjects indicated that migraine patients possess an activated nitric oxide synthesis pathway (t ₀ vs. C F=8.16,P<0.01 and F=16.2,P<0.01, respectively). As expected, in the migraine patients treated with the nitric oxide donor, a marked increase of nitrite levels was observed in sera (t ₁ vs.t ₀ P<0.05,t=3.05). In contrast, during the nitric oxide donor-induced migraine attacks a statistically significant decrease of nitrite levels in peripheral blood mononuclear cell culture supernatants was observed (t ₁ vs.t ₀ P<0.01,t=−4.03), whereas a significant increase of nitrite in total cell extracts was detected (t ₁ vs.t ₀ P<0.001,t=−6.89). These preliminary data suggest that nitric oxide could be involved in the neurovascular modifications leading to a migraine attack.     

急性一氧化碳中毒大鼠小脑组织一氧化氮及一氧化氮合酶活性的变化

目的 :研究急性一氧化碳 (CO)中毒大鼠小脑组织中一氧化氮 (NO)、一氧化氮合酶 (NOS)活性的变化 ,以探讨NO、NOS与急性CO中毒脑损伤的关系。方法 :实验用Wistar大鼠 2 6只 ,随机分为两组 :正常对照组 (C组 ) ,CO染毒组 (CO组 )。采用改良的Griess法、分光光度法分别测定小脑组织中NO、NOS活性。结果 :CO中毒后小脑组织中NO明显增高 (P <0 0 5 ) ,NOS活性明显降低 (P <0 0 1)。结论 :急性CO中毒脑组织损伤与小脑组织中NOS活性受抑制、NO含量增高有关。     

顿抑心肌背向散射积分周期变化幅度与一氧化氮及一氧化氮合酶关系的实验研究

目的　探讨顿抑心肌背向散射积分周期变化幅度 (CVIB)与一氧化氮 (NO)、一氧化氮合酶(NOS)和反映收缩功能的局部室壁增厚率 (WT)的相关关系 ,为CVIB应用于临床检测存活心肌的可靠性和准确性提供客观支持依据。方法　建立犬顿抑心肌模型 ,分别观察左冠状动脉前降支 (LAD)结扎前、结扎后 30min以及再灌注 5min、1 5min、30min后CVIB和WT的动态变化 ,检测各时间点的冠状静脉窦血NO和NOS ,并分析CVIB与WT、NO和NOS的相关性。结果　冠状动脉结扎后 30min ,各指标均显著降低 (P <0 .0 0 0 1 ) ,再灌注后均逐渐恢复 ,动态变化趋势相似 ;于再灌注后 30min ,NO和NOS完全恢复到基础值水平 ,而CVIB和WT分别只恢复到基础值的 60 .91 %± 1 1 .2 7%和 54 .54 %± 1 3 .1 7% (P <0 .0 0 0 1 ) ;并且各观察时间点的CVIB与WT、NO及NOS均有良好的相关性 ,相关系数在 0 .71 2～ 0 .842之间 ,均 P <0 .0 5。结论　CVIB不仅与反映心肌局部收缩功能的WT关系密切 ,而且与影响顿抑心肌收缩功能的NO及NOS具有良好的相关性 ,是一项检测存活心肌的准确、可靠指标     

颅脑损伤后急性期脑脊液中一氧化氮及其合成酶的动态观察

目的：检测一氧化氮（NO）及其合成酶（NOS）在颅脑损伤后急性期脑脊液中的变化,探讨了其临床意义,方法：采用检测NO的中间代谢产物亚硝酸盐来反映NO及放射强度测定法测定NOS活性,分别测定颅脑损伤后急性期脑脊液中NO和NOS变化,并行健康对照,结果：颅脑损伤后NO及NOS脑脊液中浓度第1天即增高,NO第3天达到高峰后开始下降,至第10天仍高于正常对照,NOS于损伤后第1天开始升高,至第10天仍高于正常对照组,结论：NO和NOS参与了颅脑损伤的病理生理过程,动态观察提示NO可能和颅脑损伤病情程度有关。     

高原红细胞增多症患者血清同型半胱氨酸与一氧化氮、一氧化氮合酶水平的变化

目的探讨高原红细胞增多症(HAPC)患者体内同型半胱氨酸(Hcy)与一氧化氮(NO)、一氧化氮合酶(NOS)水平的关系。方法在海拔3 300 m地区选择HAPC患者和健康人各50例进行血清Hcy、NO含量和NOS活性的检测。结果与健康人比较,HAPC患者血清Hcy水平显著升高(P<0.01),NO含量和NOS活性明显降低(P<0.01);相关分析结果表明,在HAPC患者中血清Hcy水平与NO含量和NOS活性呈显著负相关(r=-0.947、-0.925,P<0.01)。结论血清Hcy水平与NO含量和NOS活性的变化可能与HAPC的发病有关。     

地塞米松对急性颅脑损伤患者血内NOS活性和NO产量的影响

目的 了解地塞米松（ＤＭ）对急性颅脑损伤（ＡＣＩ）患者围术期血内一氧化氮合成酶（ＮＯＳ）活性和一氧化氮（ＮＯ）产量的影响。方法 ２０例ＡＣＩ患者随机分为ＤＭ治疗组（于麻醉诱导前０．４ｍｇ／ｋｇＩＶ）和对照组,用分光光度法测定血清ＮＯＳ活性和ＮＯ产量。结果 术前两组ＮＯＳ、ＮＯ均高于下沉对照组,其中ＮＯＳ有显著性差异（Ｐ〈０．０１）。ＤＭ组自麻醉诱导前至开颅手术后２４小时（Ｔ０～Ｔ５）动态观察发现,ＮＯ、ＮＯＳ自始至终呈降低趋势;而对照组则呈显著性升高（ＮＯＴ１、Ｔ５,ＮＯＳＴ５）,组间比较有显著性差异。结论 ＡＣＩ患者术前存在ＮＯＳ、ＮＯ代谢率乱,开颅手术后其含量进一步升高而加重脑缺血再灌注损伤。麻醉诱导时应用ＤＭ可显著抑制ＡＣＩ患者体内ｉＮＯＳ释放具有脑保护作用。可作为选择性ｉＤＯＳ拮抗剂在临床应用。     

Chronic headache and nitric oxide inhibitors

Sensitization of myofascial pain pathways may play an important role in the pathophysiology of chronic headache. Animal studies have shown that sensitization of pain pathways may be caused by associated with activation of neuronal nitric oxide synthase (nNOS) and the generation of nitric oxide (NO). Furthermore, it has been shown that NOS inhibitors reduce central sensitization in animal models of persistent pain. On the basis of these findings, we investigated the analgesic effect of the NOS inhibitor, N-N ^G-methyl arginine hydrochloride, and demonstrated that this drug significantly reduced headache as well as myofascial factors in patients with chronic tension-type headache. In addition, we demonstrated that infusion of the NO donor, glyceryl trinitrate, induces headache in these patients, probably by enhancing the sensitizing effect of pre-existing myofascial input. These studies strongly indicate that NO plays a crucial role in the pathophysiology of tension-type headache. We suggested that the analgesic effect of NOS inhibition in patients with chronic tension-type headache is most likely due to reduction of central sensitization at the level of the spinal dorsal horn or trigeminal nucleus, or both. Furthermore, these data suggest that inhibition of NOS may become a novel means of future treatment of chronic headache. Received: 19 February 2001 / Accepted: 11 April 2001     

Delivery and monitoring of inhaled nitric oxide

Inhaled nitric oxide is rapidly gaining popularity as a selective pulmonary vasodilator in patients with acute lung injury and pulmonary hypertension. The development of nitric oxide as a drug has bypassed the usual regulatory and commercial processes, and as a result clinicians have devised a wide range of delivery and monitoring systems. This review describes these systems, and discusses their advantages, disadvantages and safety. The monitoring of nitric oxide metabolites is also discussed.     

Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep

Objective: The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep. Design: 12 sheep were instrumented for chronic study. Six sheep received l ^G-nitro-arginine-methylester (l-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h). Measurements and results: Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of l-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of l-NAME increased mean arterial pressure (MAP) from 76.1 ± 4.2 mmHg to normal values of 95.8 ± 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 ± 3.0 to 88.6 ± 4.7 mmHg (p < 0.05). This increase in MAP was associated in the l-NAME group with a more prominent drop in cardiac index (from 10.2 ± 0.4 to 7.0 ± 0.5 l · min^–1· m^–2; p < 0.05) than in the PHP group (from 10.7 ± 0.2 to 9.3 ± 0.6 l · min^–1· m^–2). During the first 90 min of infusion, cardiac index remained lower in the l-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the l-NAME group. Conclusion: These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with l-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated. Received: 29 January 1997 Accepted: 23 October 1997