氯胺酮对大鼠脑NO/cGMP信号转导系统的影响

目的：了解氯胺酮对大鼠不同脑区一氧化氮合酶（ＮＯＳ）活性；一氧化氮（ＮＯ）产量和环鸟苷酸（ＣＧＭＰ）含量的影响。方法：ＳＤ大鼠３２只，随机分为对照组物氯胺酮组，分别腹腔注射生理盐水１０ｍｌ．ｋｇ＾－１和氯胺酮１００ｍｇ．ｋｇ＾－１，用分光光度法测定ＮＯＳ活性和ＮＯ产量，放射免疫法测定ＣＧＭＰ含量。结果：大鼠氯胺酮１００ｍｇ．ｋｇ＾－１ｉｐ能明显抑制小脑，大脑皮层、海马的ＮＯＳ活性，并明显减少上述脑     

氯胺酮对大鼠不同脑区NOS活性和NO产量的影响

目的：了争氯胺酮对大鼠脑ＮＯＳ活性和ＮＯ产量的影响。方法：１６只ＳＤ大鼠,随机分为二组,分别ｉｐ生理盐水１０ｍｌ／ｋｇ（对照组）和氯胺酮１００ｍｇ／ｋｇ。用分光光度法测定ＮＯＳ活性和ＮＯ产量。结果：大鼠ｉｐ氯胺酮１００ｍｇ／ｋｇ能明显抑制小脑、大脑皮层、海马的ＮＯＳ活性和减少ＮＯ的产量（Ｐ〈０．０５或Ｐ〈０．０１）,脑干的ＮＯ产量亦较对照组减少（Ｐ〈０．０１）,ＮＯＳ活性下降,但无统计学意义。结论     

吸入一氧化氮加强牛肺表面活性剂替代治疗的疗效

目的 研究吸入一氧化氮对牛肺泡表面活性剂替代治疗肺灌洗大鼠时疗效的影响。方法 ６４只ＳＤ大鼠经气管导管反复肺灌洗至ＰａＯ２〈１３．４ｋＰａ和ＰａＣＯ２〉８．０ｋＰａ,随机分成对照组,ＢＰＳ２５ｍｇ／ｋｇ组,ＢＰＳ５０ｍｇ／ｋｇ组,ＢＰＳ１００ｍｇ／ｋｇ组,各组分ａ,ｂ,两亚组,未吸ＮＯ为ａ,ＮＯ吸入为ｂ。观察用药后ＰａＯ２,ＰａＣＯ２,肺压力－容量环及肺实质密度变化。     

亚睡眠剂量异丙酚对小鼠痛阈的影响

目的：观察亚睡眠剂量的异丙酚对小鼠痛阈的影响。方法：ＮＩＨ小鼠１２０只，随机分为８组（每组１５只）即：对照组，注射０．９％生理盐水１０ｍｌ／ｋｇ（ＮＳ组），１０％脂肪乳剂１０ｍｌ／ｋｇ（Ｉ组），异丙酚组，注射异丙酚２．５ｍｇ／ｋｇ（Ｐ１组），５ｍｇ／ｋｇ（Ｐ２组），１０ｍｇ／ｋｇ（Ｐ３组）硫喷妥钠组，分别注射与异丙酚求证射。痛阈测定采用ＣＯ２激光痛阈测定法，结果：（１）１组与ＮＳ组比较，小鼠痛阈没     

一氧化氮在氯胺酮麻醉机制中的作用

目的：了解一氧化氮（ＮＯ）与氯胺酮麻醉作用间的关系。方法：６０只雄性昆明鼠分成４组，Ⅰ组氯胺酮１００ｍｇ／ｋｇ腹腔内注射，Ⅱ组连续３天腹腔内注射Ｎ－硝基左旋精氨酸甲酯（Ｌ－ＮＡＭＥ）５０ｍｇ／ｋｇ后，腹腔内注射氯胺酮１００ｍｇ／ｋｇ，Ⅲ组连续３天腹腔内注射左旋精氨酸３００ｍｇ／ｋｇ后，腹腔内注射氯胺酮１００ｍｇ／ｋｇ，Ⅳ组腹腔内注射氯胺酮１００ｍｇ／ｋｇ后，腹腔１小时内持续给予Ｓ－亚硝酰－Ｎ－乙酰青霉胺（ＳＮＡＰ）３０ｍｇ／ｋｇ。观察各组动物翻正反射丧失和抑制持续时间。结果：各组翻正反射丧失时间无明显差异，为１．３９～２．３０分钟。翻正反射丧失持续时间Ⅰ组４７．７１±５．１７分，Ⅱ组４７．８４±７．９９分，Ⅲ组和Ⅳ组明显比Ⅰ、Ⅱ组短，分别为３１．１４±２．４４和３２．７５±８．１４分（Ｐ＜０．０１）。结论：改变ＮＯ的生成量将影响着氯胺酮引起的小鼠翻正反射抑制的持续时间，ＮＯ在氯胺酮麻醉分子机制中起作用。     

异丙酚对大鼠中枢多巴胺再摄取的抑制作用

目的　观察异丙酚麻醉的大鼠中枢神经系统纹状体中多巴胺转运蛋白的变化,了解异丙酚麻醉时中枢多巴胺增加的调控机制。方法（１）正常ＳＤ大鼠２４只随机分为４组,分别腹腔注射异丙酚 ５０ｍｇ／ｋｇ、７５ｍｇ／ｋｇ、１００ｍｇ／ｋｇ和同容积 １０％脂肪乳剂作对照,腹腔注射后 １０分钟动物断头处死,取脑组织做脑连续切片,进行放射自显影研究;（２）ＳＤ大鼠６只,断头处死迅速取脑组织做脑连续切片,用~（１２５）Ｉ－β－ＣＴＴ为配基做放射受体结合体外抑制实验。结果　腹腔注射１００ｍｇ／ｋｇ异丙酚能明显抑制~（１２５） Ｉ－β－ＣＩＴ与纹状体中多巴胺转运蛋白结合（Ｐ＜０．０５）。体外抑制实验随异丙酚浓度增加,与脑组织多巴胺转运蛋白结合的~（１２５） Ｉ－β－ＣＩＴ的放射活性明显下降。结论异丙酚致中枢多巴胺增加与异丙酚抑制多巴胺转运蛋白对突触中多巴胺的再摄取有关。     

重组杀菌／通透性增加蛋白对内毒素休克中肝脏一氧化氮合酶的 …

目的：探讨重组杀菌／通透性增加蛋白（ｒＢＰＩ２１）对内毒素休克中肝组织一氧化氮合酶（ＮＯＳ）的影响及其意义。方法 大鼠腹腔注射大肠杆菌内毒素（１５．０ｍｇ／ｋｇ）复制内毒素休克模型，动物随机分成正常对照组、内毒素休克组和ｒＢＰＩ２１治疗组。检测肝组织ＮＯＳ活性、三磷酸鸟苷环水解酶Ｉ（ＧＴＰ－ＣＨＩ）活性及生物喋呤含量，同时还观察肝脏微循环血流灌注量的改变。结果 内毒素攻击后肝组织诱生型ＮＯＳ（ｉＮ     

异丙酚对大鼠脑突触体Na^＋,K^＋—ATP酶活性的影响

目的;了解异丙酚是否通过影响脑突触体Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶活性产生中枢抑制效应。方法：ＳＤ大鼠３０只,随机分为三组,分别腹腔注射异丙酚５０ｍｇ／ｋｇ,１００ｍｇ／ｋｇ和生理盐水１０ｍｌ／ｋｇ。结果：ｉｐ异丙酚５０ｍｇ／ｋｇ能明显抑制海马,脑干突触体的Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶活性,ｉｐ异丙酚１００ｍｇ／ｋｇ能使大脑皮层,脑干及海马突触体的Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶活性明显降低。     

左旋精氨酸对急性胰腺炎的作用

探讨左旋精氨酸（Ｌ－Ａｒｇ）在大鼠急性水肿性胰腺炎（ＡＥＰ）中的作用。方法观察倍数剂量Ｌ－Ａｒｇ治疗ＡＥＰ大鼠后,血浆和胰组织一氧化氮（ＮＯ）浓度、血浆淀粉酶、平均动脉压（ＭＡＰ）、胰组织病理的变化。结果ＡＥＰ大鼠血浆、胰组织ＮＯ浓度明显降低,Ｌ－Ａｒｇ５０、１００ｍｇ／ｋｇ升高血浆、胰组织ＮＯ浓度,改善了大鼠ＡＥＰ;Ｌ－Ａｒｇ８００、１６００ｍｇ／ｋｇ体重使ＮＯ浓度过度升高,加重ＡＥＰ成为急性出血坏死性胰腺炎（ＡＨＮＰ）;胰组织病理评分与血浆、胰组织ＮＯ浓度呈正相关。Ｌ－Ａｒｇ对ＭＡＰ的影响较小。血浆淀粉酶除８００ｍｇ／ｋｇ体重组明显降低外,其余各组间无明显差异。结论Ｌ－Ａｒｇ因升高ＮＯ浓度而参与了大鼠ＡＥＰ的病理过程。     

诱导性一氧化氮合酶抑制药对感染性休克治疗作用的观察

目的：评价诱导性一氧化氮合酶（ｉＮＯＳ）抑制药氨基胍（ＡＧ）的抗感染性休克作用。方法：杂种犬（８￣１２ｋｇ）２小时内静滴内毒素（ＬＰＳ，１ｍｇ／ｋｇ）后随机分为对照（ｎ＝６）和治疗疗组。治疗组在ＭＡＰ下降后２小时分别静注Ｌ－Ｎ位硝基精氨甲酯（Ｌ－ＮＡＭＥ，ｎ＝６．３０ｍｇ／ｋｇ）和ＡＧ（ｎ＝Y６。２０ｍｇ／ｋｇl）。结果：静注后的ＬＰＳ后１小时在ＮＯ升高同时ＭＡＰ明显下降。ＳＶＲ和尿量明显减少。给予     

异丙酚对大鼠脑突触体Na~ ,K~ -ATP酶活性的影响

目的 :了解异丙酚是否通过影响脑突触体Na ,K ATP酶活性而产生中枢抑制效应。方法 :SD大鼠 30只 ,随机分为三组 ,分别腹腔注射 (ip)异丙酚 5 0mg/kg、10 0mg/kg和生理盐水 10ml/kg。结果 :ip异丙酚 5 0mg/kg能明显抑制海马、脑干突触体的Na ,K ATP酶活性 (P <0 0 1) ,ip异丙酚 10 0mg/kg能使大脑皮层、脑干及海马突触体的Na ,K ATP酶活性明显降低 (P <0 0 1)。异丙酚 10 0mg/kg组的大脑皮层、脑干及海马突触体的Na ,K ATP酶活性均明显低于异丙酚 5 0mg/kg组 (P <0 0 5或P <0 0 1)。结论 :异丙酚对中枢神经系统的抑制作用 ,可能与其抑制脑突触体Na ,K ATP酶活性有关     

静脉麻醉药抑制利多卡因致大鼠惊厥作用的比较

目的比较静脉麻醉药丙泊酚、依托咪酯、咪达唑仑及硫喷妥钠拮抗利多卡因致大鼠惊厥的作用。方法雄性Wistar大鼠36只,体重(250±20)g,随机均分为六组:空白对照组(C组)、利多卡因组(L组:利多卡因4mg·kg-1·min-1)、利多卡因+丙泊酚组(P组:利多卡因+丙泊酚12.5mg/kg)、利多卡因+依托咪酯组(E组:利多卡因+依托咪酯1.85mg/kg)、利多卡因+咪达唑仑组(M组:利多卡因+咪达唑仑0.65mg/kg)和利多卡因+硫喷妥钠组(T组:利多卡因+硫喷妥钠30.85mg/kg),惊厥后2h处死大鼠,取出脑组织分离双侧海马,一侧用于检测c-fos阳性细胞蛋白的表达。另一侧用于测定一氧化氮(NO)含量及一氧化氮合酶(NOS)活性。结果除C组外,其它五组大鼠均出现了惊厥,给予静脉麻醉药抑制惊厥,五组惊厥持续时间差异无统计学意义。L、P、E、M和T组c-fos阳性细胞表达、NO含量和NOS活性显著高于C组(P<0.05);P、E、M和T组c-fos阳性细胞表达、NO含量及NOS活性均显著降低于L组(P<0.05);M、T组c-fos阳性细胞表达、NO含量及NOS活性显著低于P、E组(P<0.05)。结论静脉麻醉药咪达唑仑、丙泊酚、依托咪酯及硫喷妥钠均可有效抑制利多卡因致惊厥作用,其中咪达唑仑与硫喷妥钠效果更显著。     

异丙酚对顺行性遗忘和逆行性遗忘的影响

目的 观察老龄小鼠异丙酚麻醉后对学习记忆及遗忘的影响。方法 选择正常昆明小鼠进行被动逃避暗实验。分别于训练前１５ｍｉｎ腹腔注射异丙酚（５０ｍｇ／ｋｇ和１００ｍｇ／ｋｇ）和训练后３０ｍｉｎ、３ｈ腹腔注射异丙酚（１００ｍｇ／ｋｇ和２００ｍｇ／ｋｇ）,记录训练后２４ｈ的逃避电击进入暗室的潜伏期及５ｍｉｎ内的错误次数;处死动物。用放射免疫的方法检测小鼠脑中胆碱乙酰化酶的活性。结果 正常小鼠训练后２４ｈ易于     

Inhaled nitric oxide and nifedipine have similar effects on lung cGMP levels in rats.

Inhaled nitric oxide (NO) may downregulate the endogenous NO/cyclic guanosine monophosphate (cGMP) pathway, potentially explaining clinical rebound pulmonary hypertension. We determined if inhaled NO decreases pulmonary cGMP levels, if the possible down-regulation is the same as with nifedipine, and if regulation also occurs with the cyclic adenosine monophosphate (cAMP) pathway. Rats were exposed to 3 wk of normoxia, hypoxia (10% O2), or monocrotaline (MCT; single dose = 60 mg/kg) and treated with either nothing (control), inhaled NO (20 ppm), or nifedipine (10 mg x kg(-1) x day(-1). The lungs were then isolated and perfused with physiologic saline. Perfusate cGMP, prostacyclin, and cAMP levels were measured. Perfusate cGMP was not altered by inhaled NO or nifedipine in normoxic or MCT rats. Although hypoxia significantly increased cGMP by 128%, both inhaled NO and nifedipine equally prevented the hypoxic increase. Inhibition of the NO/cGMP pathway with N(G)-nitro-L-arginine methyl ester (L-NAME) decreased cGMP by 72% and 88% in normoxic and hypoxic lungs. Prostacyclin and cAMP levels were not altered by inhaled NO or nifedipine. L-NAME significantly decreased cGMP levels, whereas inhaled NO had no effect on cGMP in normoxic or MCT lungs, suggesting that inhaled NO does not inhibit the NO/cGMP pathway. Inhaled NO decreased cGMP in hypoxic lungs, however, nifedipine had the same effect, which indicates the decrease is not specific to inhaled NO. IMPLICATIONS: High pulmonary pressure after discontinuation of inhaled nitric oxide (NO) may be secondary to a decrease in the natural endogenous NO vasodilator. This rat study suggests that inhaled NO either does not alter endogenous NO or that it has similar effects as nifedipine.     

Effect of exogenous l-arginine and ageing on NO and ET-1 in penile tissue of rat

The aim of this study was to investigate the effect and significance of l ‐arginine and ageing on nitric oxide (NO)‐cyclic guanosine monophosphate (cGMP) pathway and ET‐1 in penile tissue of rats. The different months old rats were divided into control group and experiment group randomly, the content of NO, cGMP, the changes of activity of Nitrous Oxide Systems (NOS) and the content of endothelin‐1(ET‐1) in penile tissue were determined. Along with ageing, NO and the activity of NOS in penile tissue increased at first and then decreased (P < 0.001). The content of cGMP reduced obviously (P < 0.001), the content of ET‐1 had a tendency to increase, and the ratio of ET‐1/NO increased significantly (P < 0.001 or P < 0.01). After feeding rats with l ‐arginine for some time, both the activity of NOS and the content of cGMP increased significantly in penile tissue (P < 0.001), while there was no obvious change in the content of ET‐1. Our study shows that whether the smooth muscle cells relax or contract might be decided by the content of cGMP and value of ET‐1/NO in penile tissue. l ‐arginine had significant effect on increasing the activity of NOS and the content of NO and cGMP, indicating that l ‐arginine has potential clinical value to be used in treating ED.     

异丙酚对大鼠肺一氧化氮合酶活性的影响

目的 了解异丙酚对大鼠肺一氧化氮合酶(NOS)活性的影响,探讨异丙酚对肺血管、支气管扩张作用的机理。方法40只SD大鼠,随机分为异丙酚组(n=20)、对照组(n=20),分别腹腔注射等容积异丙酚(1ml·kg-1,即100mg·kg-1)和生理盐水(10ml·kg-1)。异丙酚组待鼠翻正反射消失后,经尾缘静脉泵以异丙酚10mg·kg-1·h-1,20min后处死,对照组鼠腹腔注射20min后处死。检测支气管肺泡灌洗液NO水平、肺组织匀浆中NOS酶活性、NO水平及内皮型NOS(eNOS)、神经型NOS(nNOS)在肺内的表达与分布(免疫组化法)。结果 异丙酚组支气管灌洗液和肺组织匀浆中NO水平均明显高于对照组(P<0.01),肺组织匀浆中NOS酶活性也明显大于对照组(P<0.01)。异丙酚组肺血管内皮细胞nNOS和eNOS、支气管粘膜上皮细胞nNOS染色表达强阳性。结论 异丙酚可以刺激肺中NOS活性,升高肺内内源性NO水平,在异丙酚的扩张肺血管、支气管中发挥一定的作用。     

Ketamine Inhibits Glutamate-, N-Methyl-D-Aspartate-, and Quisqualate-stimulated cGMP Production in Cultured Cerebral Neurons

Background: Glutamatergic signaling has been linked to the recently discovered neurotransmitter/neuromodulator nitric oxide (NO), and several classes of anesthetics block some step in glutamatergic signaling. This study was designed to determine whether or not ketamine would prevent NO-dependent cGMP production stimulated by glutamate (GLU) and the GLU analogs NMDA, quisqualate (QUIS), and kainate (KAIN).

Methods: Primary cultures of cortical neurons and glia (prepared from 16-day gestational rat fetuses) were used after 12-16 days in culture. Reactions were carried out in magnesium-free buffer containing 100 micro Meter 3-isobutyl-l-methylxanthine, and cGMP content of cultures was used as a bioassay of NO production.

Results: Cyclic GMP production stimulated by sodium nitroprusside (100 micro Meter) occurred predominately in neurons and not in glia. Neurons were spontaneously active in these cultures; basal cGMP production was decreased by 50% in the presence of 1 micro Meter tetrodotoxin (TTX). Glutamate (100 micro Meter), NMDA (100 micro Meter), QUIS (300 micro Meter), and KAIN (100 micro Meter) each increased cGMP content of neuronal cultures. L-NMMA (100 micro Meter), a NO synthase inhibitor, prevented the stimulation of cGMP production by GLU or its analogs. Pretreatment with MK-801 (1 micro Meter) or ketamine (10-100 micro Meter) inhibited GLU-, NMDA-, and QUIS-stimulated cGMP production. Quisqualate-stimulated responses were the most sensitive to inhibition by ketamine and NMDA-stimulated responses were the least sensitive to inhibition. MK-801 and ketamine did not significantly inhibit KAIN-stimulated cGMP production. CNQX (10 micro meter) blocked KAIN-stimulated cGMP production only.     

Propofol stimulates ciliary motility via the nitric oxide-cyclic GMP pathway in cultured rat tracheal epithelial cells

BACKGROUND: Airway ciliary motility is impaired by inhaled anesthetics. Recent reports show that nitric oxide (NO) induces upregulation in ciliary beat frequency (CBF), and others report that propofol, an intravenous anesthetic, stimulates NO release; this raises the possibility that propofol increases CBF by stimulating the NO-cyclic guanosine monophosphate (cGMP) signal pathway. In this study, the authors investigated the effects of propofol on CBF and its relation with the NO-cGMP pathway using the pharmacologic blockers NG-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor; 1H-[1,2,4]oxidazole[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor; and KT5823, a cGMP-dependent protein kinase inhibitor, in cultured rat tracheal epithelial cells. METHODS: Rat tracheal tissues were explanted and cultured for 3-5 days. Images of ciliated cells were videotaped using a phase-contrast microscope. Baseline CBF and CBF 25 min after exposure to propofol or blocker were measured using video analysis. RESULTS: Vehicle (0.1% dimethyl sulfoxide; n = 11) increased CBF by 0.2 +/- 1.7% (mean +/- SD) from baseline. Propofol stimulated CBF significantly (P < 0.01) and dose dependently (1 microM, 2.0 +/- 1. 9%, n = 6; 10 microM, 8.2 +/- 6.7%, n = 9; 100 microM, 14.0 +/- 4.7%, n = 10). Intralipid (0.05%), the clinical vehicle of propofol, did not affect CBF (-0.2 +/- 2.2%; n = 5). The enhancement of CBF with use of 100 microm propofol was abolished (P < 0.01) by coadministration of 10 mmicroM l-NMMA (2.4 +/- 3.6%; n = 5), 100 microM ODQ (-0.3 +/- 2.2%; n = 6) or 30 microM KT5823 (-0.1 +/- 4. 1%; n = 8). l-NMMA, ODQ, or KT5823 alone did not change CBF. CONCLUSIONS: These results show that propofol stimulates CBF viathe NO-cGMP pathway in rat tracheal epithelial cells, suggesting a possible advantage of propofol in decreasing respiratory risk.     

在大鼠切口疼痛模型中鞘内新斯的明对脊髓NO/cGMP信号转导系统的影响

目的 了解大鼠切口疼痛模型中鞘内（IT）新斯的明（NEO）对脊髓一氧化合酶（NOS）活性、一氧化氮（NO）产量和环鸟苷酸（cGMP）含量的影响。方法 雄性64只,随机分为四组,每组16只：假手术组（组I0、术前30minIT0．9％氯化钠20μl组（组Ⅱ）、术后30minITNEO10μg组（组Ⅲ）和术前30minITNEO10μg组（组Ⅳ）。按Brennan法制成切口疼痛模型,以累积疼痛评分确定疼痛行为。在术后2h断头取腰段脊髓,以分光光度法测定NOS活性、NO产量;放射免疫法测定cGMP含量／结果 组Ⅲ和组Ⅳ大鼠的累积评分均明显低于组Ⅱ（P＜0．01）。组Ⅱ的脊髓NOS活性、NO产量和cGMP含量均较组Ⅰ明显升高（P＜0．01）。组Ⅳ的脊髓NOS活性、NO产量和cGMP含量均较组Ⅰ明显升高（P＜0．01）。组Ⅳ的脊髓NOS活性、NO产量和cGMP含量均较组Ⅱ明显降低（P＜0．05或0．01）。而两用药组上述指标比较以及用药组与组I比较均无明显差别（P＞0．05）。结论 在大鼠切口疼痛模型中,术前IT NEO的抗伤害作用可能与NO／cGMP信号转导系统有关。