CNQX对电刺激隐神经诱发大鼠扣带回前部神经元c-Fos基因表达的影响

目的阐明伤害性电刺激隐神经(saphenous nerve,SN)能否引起扣带回前部(anterior cingulategyrus,ACG)神经元c-Fos基因表达及其发生机制。方法用免疫组化方法研究伤害性电刺激SN后不同时间,ACG神经元c-Fos基因表达的变化,以及尾静脉注射α-氨基3-羟基5-甲基4-异恶唑丙酸/海人藻氨酸(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid/kainate,AMPA/kainate)受体拮抗剂受体是谷氨酸受体之一,6-氰基-7-硝基喹喔啉-2,3-二酮(6-cyano-7-nitroquinoxaline-2,3-dike-tone,CNQX)对该变化的影响。结果伤害性电刺激SN后30 min ACG神经元Fos蛋白表达明显增加,60 min增加最明显,120 min后开始消退;并且尾静脉注射CNQX拮抗了伤害性电刺激SN引起的ACG神经元Fos蛋白表达的显著增加。结论伤害性电刺激SN能够引起ACG神经元Fos蛋白表达的显著增加,这种表达呈时间依赖性,提示ACG存有SN代表区,能够感受SN传入的伤害性信息;CNQX拮抗了伤害性电刺激SN引起的ACG神经元Fos蛋白表达的显著增加,提示AMPA/kainate受体参与此过程。     

CNQX对伤害性刺激隐神经诱发大鼠脊髓Fos蛋白表达的影响

目的 探讨伤害性刺激隐神经（SN）能否诱发脊髓神经元Fos蛋白表达及发生机制.方法 应用免疫组化方法观察伤害性刺激SN和尾静脉注射谷氨酸非NMDA受体拮抗剂（CNQX）后诱发脊髓神经元Fos蛋白表达的变化.结果 伤害性刺激SN后,诱导脊髓神经元Fos蛋白表达显著增强,CNQX拮抗了Fos蛋白表达的显著增强.结论 以伤害性刺激SN模拟躯体痛后,CNQX拮抗了伤害性刺激SN引起的脊髓神经元Fos蛋白表达的显著增加,表明非NMDA受体在躯体痛的调控中起到了重要的作用.     

吗啡、MK-801对电刺激隐神经引起大鼠ACG多巴胺含量增高的影响

目的研究皮下注射吗啡、静脉注射N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体拮抗剂5-甲基二氢丙环庚烯马来酸(MK-801)对电刺激隐神经(saphenous nerve,SN)引起大鼠扣带回前部(anterior cingulate gyrus,ACG)多巴胺含量增高的影响,以及MK-801对吗啡作用的影响。方法应用高效液相色谱-电化学检测技术进行实验研究。结果电刺激SN引起ACG多巴胺含量显著增高;皮下注射吗啡抑制电刺激SN引起的ACG多巴胺含量的显著增高;静脉注射MK-801能够拮抗电刺激SN引起的ACG多巴胺含量的显著增高,并且能够增强吗啡抑制电刺激SN引起的ACG多巴胺含量的显著增高。结论 SN传导的伤害性信息能够到达ACG,激活ACG多巴胺能神经元,释放多巴胺,谷氨酸NMDA受体参与此过程;吗啡抑制ACG多巴胺能神经元的活动;MK-801增强吗啡的抑制作用。     

内吗啡肽—1的镇痛作用

目的：研究内吗啡肽－1（EM－1）的镇痛作用。方法：采用电刺激鼠尾－嘶叫法、扭体法、佐剂性关节炎以及神经源性疼痛等多种疼痛模型,观察腹腔注射EM－1的镇痛作用,并和脊髓蛛网膜下腔注射和侧脑室注射EM－1的镇痛作用进行比较。结果：1）EM－1能剂量依赖地提高大鼠电刺激鼠尾－嘶叫法的痛阈;能抑制醋酸引起的小鼠扭体反应;在佐剂性关节炎所致的炎症性痛觉过敏及坐骨神经部分结扎所引起的神经源性痛觉过敏中,EM－1与有镇痛作用。2）中枢给EM－1的镇痛作用比外击给药出现得较快,而且较强。3）阿片受体拮抗选择性拮抗剂cyprodime也能翻转EM－1的镇痛作用;反复给予EM－1具有确切的镇冯作用,其镇痛作用由中枢μ阿片受体介导。     

BoNT-A对慢性坐骨神经结扎大鼠疼痛行为学及脊髓中Fos蛋白的影响

目的 探讨肉毒毒素A(BoNT-A)对神经病理性疼痛大鼠疼痛行为学及脊髓背角Fos蛋白表达的影响.方法 建立雄性SD大鼠慢性坐骨神经结扎(CCI)疼痛模型,CCI术后第3天开始,同侧肢体足底皮下注射BoNT-A 30 U/kg和等容积生理盐水,给药前、给药后1、3、5、7、14 d,采用von-Frey纤维细丝机械刺激法和热辐射刺激法评定大鼠机械刺激缩足反射阈值(MWT)和热刺激缩足反射潜伏期(TWL),观察大鼠疼痛行为学变化,根据变化结果,给药后第5天取相应脊髓节段标本,运用免疫组织化学法观察脊髓背角Fos蛋白表达.结果 CCI神经病理性疼痛模型大鼠建立后,CCI组同侧MWT和TWL均明显降低,且脊髓水平Fos蛋白表达明显增多;同侧足底注射BoNT-A 30 U/kg后,其MWT和TWL,均显著增加,脊髓水平Fos蛋白表达明显减少.结论 足底注射BoNT-A抑制脊髓水平Fos蛋白的表达,能减轻神经病理性疼痛模型大鼠的机械性触诱发痛和热痛觉过敏.     

吗啡依赖大鼠长期戒断后的觅药行为与伏膈核Fos表达

目的 :研究吗啡依赖大鼠长期停药后的觅药行为和伏膈核各亚区 (外壳区、核心区 )的Fos蛋白表达。方法 :大鼠皮下注射吗啡使其成瘾 ,停药 2月后进行条件性位置偏爱试验 ,并检测伏膈核核心区和外壳区的Fos蛋白表达。结果 :吗啡预处理组大鼠的位置偏爱效应明显强于盐水预处理组 ,在伏膈核核心区的Fos蛋白表达显著高于对照组。结论 :位置偏爱行为与吗啡相关环境刺激引起伏膈核核心区的激活有关 ,预先慢性吗啡处理大鼠在吗啡诱导下对药物相关环境的偏爱强于预先盐水处理大鼠     

鞘内注射可乐定对甲醛致痛大鼠脊髓c-fos表达的影响

<正>本研究通过对甲醛致痛大鼠蛛网膜下腔给予可乐定,观察大鼠伤害性行为学反应、脊髓背角Fos蛋白表达的改变,旨在探讨可乐定在甲醛致痛模型中的作用及可能的作用机制。1材料与方法     

NO介导吗啡戒断大鼠脊髓Fos蛋白和NMDA_(1A)受体mRNA表达的增加

目的:观察NO在纳洛酮催促吗啡戒断大鼠脊髓神经元活动变化中的作用。方法:采用Fos免疫组织化学、NADPH-d组织化学、Fos/NADPH-d双标、鞘内注射、反义寡核苷酸和RT-RCR技术。结果:急性应用纳洛酮和慢性应用吗啡对大鼠脊髓Fos蛋白及NADPH-d阳性神经元表达无明显影响,二者也无Fos/NADPH-d双标神经元表达;纳洛酮催促吗啡戒断大鼠脊髓Fos蛋白、NADPH-d阳性神经元、纤维和终末表达明显增加,且出现Fos/NADPH-d双标神经元表达。预先鞘内注射nNOS反义寡核苷酸明显降低吗啡戒断症状评分,减少吗啡戒断大鼠脊髓Fos蛋白及NMDA_(1A)R mRNA表达。结论:NO介导吗啡戒断大鼠脊髓Fos和NMD_(1A)R mRNA表达的增加。     

鞘内注射氯胺酮对内脏痛大鼠远位触液神经元Fos蛋白表达的影响

目的观察鞘内注射氯胺酮对内脏痛大鼠远位触液神经元(dCSF-CN)Fos蛋白表达的影响。方法 SD大鼠侧脑室注射霍乱毒素亚单位B与辣根过氧化物酶复合物(CB-HRP)示踪标记dCSF-CN。48h后氯胺酮(K)组(n=10)鞘内注射氯胺酮50μg,人工脑脊液(C)组(n=10)鞘内注射等体积人工脑脊液。两组均在乙状结肠壁注射甲醛制作内脏痛模型。进行各时间点疼痛学评分,免疫组织化学法检测Fos蛋白在dCSF-CN中的表达。结果与C组相比,K组大鼠各时间点疼痛学评分降低(P<0.01),dCSF-CN中Fos蛋白表达下降(P<0.01)。K组未见CB-HRP/Fos双标记神经元。结论鞘内注射氯胺酮可以降低大鼠内脏痛反应,减少dCSF-CN中Fos蛋白的表达。     

催产素对甲基苯丙胺引起的小鼠前额叶皮层和海马内N-甲基-D-天冬氨酸受体亚型1蛋白表达变化的影响

目的研究脑室注射催产素对甲基苯丙胺引起的小鼠前额叶皮层和海马内谷氨酸N-甲基-D-天冬氨酸受体亚型1(NMDAR1)蛋白表达变化的影响,为探讨催产素拮抗甲基苯丙胺精神依赖作用的中枢机制提供实验依据。方法分别取经急性和慢性甲基苯丙胺处理的小鼠的前额叶皮层和海马,采用Western Blot分析方法检测催产素对NMDAR1蛋白表达的影响。结果催产素可以显著拮抗急性给予甲基苯丙胺及复吸甲基苯丙胺引起的小鼠前额叶皮层NMDAR1蛋白表达的增高;可以显著抑制甲基苯丙胺戒断时引起的小鼠前额叶皮层NMDAR1蛋白表达的降低;急性及慢性甲基苯丙胺处理对小鼠海马内NMDAR1蛋白表达没有显著性影响。结论用甲基苯丙胺处理对小鼠前额叶皮层部位NMDAR1蛋白表达的影响较大;催产素可以拮抗甲基苯丙胺引起的前额叶皮层部位NMDAR1蛋白表达的变化。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.