STZ引起的短期Ⅰ型糖尿病对大鼠背根神经节CGRP mRNA水平的影响

糖尿病时,感觉神经元和血浆中的降钙素基因相关肽(calcitonin gene-related peptides, CGRP)会发生改变,血管对CGRP的反应性减弱[1],CGRP的改变是糖尿病时疼痛增加和发生损伤性炎症的重要原因[2].但关于短期糖尿病状态下,CGRP mRNA的动态变化如何,尚无文献报道.本文着重探讨短期糖尿病背根神经节(dorsal root ganglion, DRG)中CGRP mRNA的早期动态变化.     

电损毁伏核核部或壳部对大鼠吗啡奖赏效应及其性功能的影响

目的:研究直流电损毁伏核(nucleus accumbens NAc)核部及壳部对大鼠吗啡奖赏效应及其性功能的影响。方法:建成♂大鼠吗啡条件性位置偏爱(5mg.kg-1,ip)后,用直流电损毁或假损毁其NAc核部或壳部。损毁术后7d及10d时再次测试大鼠位置偏爱的表达。12d时给予大鼠小剂量吗啡(2.5mg.kg-1,ip)后,再次进行测试。之后,让大鼠进行一轮交配,记录性功能相关指标。结果:假损毁组大鼠在各时间点测试时,均可稳定表达已形成的吗啡条件性位置偏爱,而核部及壳部损毁组大鼠在术后7d及10d测试时未表达对吗啡伴药侧的偏爱,但12d给予小剂量吗啡后,壳部损毁组动物再次表达出对伴药侧的偏爱,而核部损毁组则仍未表达任何偏爱;各组大鼠的性功能未受影响。结论:NAc核部损毁能抑制大鼠吗啡CPP的重建,而壳部损毁则不能,且该损毁手术对大鼠的性功能无影响。     

中枢吗啡预处理对心脏缺血后大鼠海马CaM、血浆CGRP以及下丘脑室旁核和心肌P物质表达的影响

目的探讨侧脑室内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤的影响及可能的信号机制。方法建立模型大鼠,随机分为两个部分:①分为4组,每组6只:对照组(CON组),在缺血/再灌注前30 min内,侧脑室内微量泵注射0.9%生理盐水5 min,停止注射5 min,重复3次;预处理组(MPC组),在缺血/再灌注前30 min内,侧脑室内注射吗啡(1μg.kg-1)5 min,停止5 min,重复3次;钙调蛋白抑制剂三氟拉嗪(trifluoperazine,TFP)+预处理组(TFP+MPC组),在吗啡预处理前10 min一次侧脑室内给予TFP(浓度为20 g.L-1)5μl;另设TFP自身对照组(TFP组)。②分为3组,每组6只:假手术组(Sham组),CON组和MPC组均同第一部分。观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积、心肌梗死面积以IS/AAR表示;检测血浆降钙素基因相关肽(calcitonin gene related peptide,CGRP);测定海马组织钙调蛋白;测定下丘脑室旁核、心肌缺血区和非缺血区P物质的表达。结果与CON组相比,MPC组的IS和IS/AAR均明显下降(P<0.01),TFP+MPC组分别与TFP组和CON组相比差异无显著性(P>0.05),而均明显高于MPC组(P<0.01);CON组分别与Sham组和MPC组相比,其下丘脑室旁核、心肌缺血区和非缺血区P物质表达均明显增高(P<0.01,P<0.05);MPC组血浆降钙素基因相关肽CGRP水平与海马钙调蛋白的表达均明显高于其它各组(P<0.01)。结论侧脑室内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤具有保护作用,其机制可能与钙调蛋白介导释放CGRP和痛觉的干预有关。     

STz引起的短期I型搪尿病对大鼠背根神经节CGRP mRNA水平的影响

糖尿病时，感觉神经元和血浆中的降钙素基因相关肤(calcitonin gene-gelated peptides,CGRP)会发生改变，血管对CGRP的反应性减弱^[1]，CGRP的改变是糖尿病时疼痛增加和发生损伤性炎症的重要原因^[2]。但关于短期糖尿病状态下，CGRP mRNA的动态变化如何，尚无文献报道。本文着重探讨短期糖尿病背根神经节(dorsal root ganglion,DRG)中CGRP mRNA的早期动态变化。     

CGRP、K_(ATP)通道和脊神经在鞘内注射吗啡预处理减轻大鼠心肌缺血后损伤中的作用

目的探讨降钙素基因相关肽(CGRP)、ATP敏感性钾离子通道(KATP通道)和脊神经在鞘内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤中的保护作用。方法♂SD大鼠60只,建立鞘内置管和心肌缺血/再灌注损伤模型,随机分为10组,每组6只:对照组(CON,生理盐水)、二甲亚砜组(DMSO,GLI的溶剂)、CGRP8-37组(CGRP受体阻滞剂,3nmol.kg-1)、格列苯脲组(GLI,KATP通道阻滞剂,0.3 mg.kg-1)、利多卡因组(LID,1%盐酸利多卡因10μl)、鞘内注射吗啡预处理组(MPC,3×1μg.kg-1)、CGRP8-37+MPC组、GLI+MPC组、LID+MPC组、GLI+LID组。观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积、心肌梗死面积以IS/AAR表示。结果与CON组比较,MPC组、LID组、LID+MPC组和GLI+LID组的IS和IS/AAR均明显下降(P<0.05,P<0.01);与MPC组比较,CGRP8-37+MPC组、GLI+MPC组和LID+MPC组的IS和IS/AAR均明显增加(P<0.01)。结论外周CGRP的释放、KATP通道和脊神经可能参与了鞘内注射吗啡预处理减轻大鼠心肌缺血后损伤的作用。     

胫骨神经损伤对骨折愈合过程中CGRP表达的影响

目的研究胫骨神经损伤后大鼠胫骨骨折骨痂中CGRP的表达。方法将SD大鼠40只分为2组,实验组20只和对照组20只,分别于骨折术后7、14、21、28 d处死大鼠,在骨折处取骨痂标本,观察胫骨骨折愈合过程中胫骨神经损伤时降钙素基因相关肽(CGRP)表达变化。结果对照组骨折后7 d在愈伤组织中即可见到降钙素基因相关肽(CGRP)阳性神经纤维,沿血管分布,14²1 d在编织骨边缘有大量的CGRP阳性神经纤维,28 d时仍有较高水平。研究组除骨折后7 d骨痂中见CGRP阳性表达外,以后骨痂中CGRP表达逐渐下降,其中术后14、21、28 d两组组间CGRP表达量比较差异均有统计学意义(P<0.05)。结论在骨折愈合过程中,骨折合并周围神经损伤不利于骨折愈合,周围神经对骨折的愈合起着重要的调节作用。     

心肌肥厚大鼠外周血中CGRP和IL-6的表达变化

目的：探讨大鼠心肌肥厚形成过程中外周血降钙素基因相关肽（CGRP）和白介素-6（IL-6）的变化及意义。方法：参照Ander－son方法制作压力负荷性心肌肥厚大鼠模型,采用放免法检测大鼠不同时间点外周血CGRP、IL-6的浓度,电子天平称量左心室重,计算心重指数（LVW/BW）。结果：①模型组IL-6的浓度高于对照组（P<0.05）,与心重指数呈正相关;②模型组CGRP的浓度均低于对照组（P<0.05）,与心重指数呈负相关。结论：①伴随着心肌肥厚的发生发展,外周血中IL-6浓度增加;CGRP浓度减少;②CGRP和IL-6与心肌肥厚关系密切。     

首乌降压胶囊对肾性高血压大鼠血浆ANP、CGRP的影响

首乌降压胶囊是根据十多年的临证经验，结合临床高血压病的病因病机特点研制而成，由制首乌、枸杞子、珍珠粉、钩藤、怀菊花、夏枯草、怀牛膝、川芎、丹参、泽泻、地龙等组成。前期的临床疗效观察表明，首乌降压胶囊对高血压病具有明显的降压疗效，并有改善血液流变学指标，明显降低全血黏度、血浆黏度的作用。为进一步验证其降压效果，探讨其作用机理，笔者对其降压及对血浆心钠素(ANP)、降钙素基因相关肽(CGRP)的影响进行实验观察，并与卡托普利对照比较，现报告如下。     

高压氧对脑出血患者血浆内NPY、CGRP的影响

目的高压氧治疗高血压脑出血后检测血浆内神经肽Y（NPY）、降钙素基因相关肽（CGRP）的变化,探讨神经肽与脑出血的相关性。方法 60例脑出血急性期患者随机分成高压氧治疗组和常规治疗组,每组30例,30例健康体检者作为对照组,高压氧治疗组在常规治疗基础上加用高压氧治疗方案,观察三组患者血浆NPY、CGRP的变化情况。结果两个治疗组较对照组患者血浆NPY、CGRP水平均升高,差异有统计学意义（P〈0.05）,高压氧治疗组较常规治疗组患者血浆NPY、CGRP水平明显降低,差异有统计学意义（P〈0.05）。结论高压氧可以显著降低NPY、CGRP水平,改善脑内血液循环,促进血脑屏障恢复,是治疗脑出血的有效措施。     

静脉注射降钙素基因相关肽对大鼠血压和心率的影响

目的 观察静脉注射国产降钙素基因相关肢(CGRP)对大鼠血压和心率的影响。方法 给大鼠注射不同剂量的降钙素基因相关肢，观察其对正常血压和肾上腺素所致的血压升高以及心率的影响：同时观察静脉注射依那普利(1．5mg／kg)对肾上腺素引起的血压升高的作用。结果 静脉注射CGRP可明显降低大鼠血压并具有剂量效应关系，而对心率无影响：依那普利可显低肾上腺素所致的血压升高。结论 降钙素基因相关肢可显降低大鼠血压．但对心率无明显影响。     

慢性脑缺血大鼠Nogo-A和NgR表达的变化

目的 探讨大鼠海马区Nogo-A和NgR表达在慢性脑缺血的不同时间点的动态变化.方法 大鼠随机分为假手术组、15、30和60 d模型组;采用双侧颈总动脉永久结扎建立慢性脑缺血模型;Morris水迷宫试验检测行为学变化;免疫组化染色检测Nogo-A和NgR的表达变化.结果 Nogo-A和NgR免疫反应阳性细胞数模型组比假手术组均增多(P＜0.01),与行为学改善基本相符.结论 慢性脑缺血造成Nogo-A和NgR表达持续升高可能是成年哺乳动物损伤后神经再生障碍的重要原因之一.     

Effects of morphine in the nucleus accumbens on stimulant-induced locomotion.

This study assessed the effects of morphine in the nucleus accumbens on motility elicited by dopaminergic and other classes of drugs, using locomotor activity as the measured response. Dopaminergic stimulants, d-amphetamine (10 micrograms) or dopamine (20 micrograms, 2 hours after nialamide, 200 mg/kg, IP) induced large increases in locomotor activity when injected into the nucleus accumbens. This response was blocked by coadministration of morphine (5 micrograms). The hypermotility response elicited by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 0.5 micrograms), an excitatory amino acid agonist, was also abolished by coadministration of morphine. Increasing the dose of AMPA to 1.5 micrograms partially overcame the morphine block, while increasing the dose of amphetamine to 50 micrograms did not. In other experiments, morphine (5 micrograms) injected into the nucleus accumbens blocked the hypermotility elicited by systemic caffeine (10 mg/kg, SC) or scopolamine (0.5 mg/kg, SC) or intra-accumbal MK-801 (5 micrograms). However, picrotoxin (0.15 or 0.5 microgram) injected into the nucleus accumbens elicited a hypermotility that was not attenuated by coinjection of morphine (5 or 10 micrograms). These data demonstrate that opiate and dopaminergic pathways have competing actions on the regulation of locomotion in the nucleus accumbens. Furthermore, the results with combinations of picrotoxin and morphine suggest the presence of two distinct locomotor pathways or a GABA receptor site "downstream" from the morphine site in a single pathway.     

缺氧缺血新生鼠脑损伤后银杏叶对Nogo-A蛋白表达的影响

目的 探讨银杏叶对新生大鼠缺氧缺血性脑损伤后Nogo-A表达的影响.方法 72只7d龄SD大鼠随机分为银杏叶治疗组、对照组和假手术组,应用免疫组化的方法观察银杏叶对脑组织Nogo-A表达的影响.结果 脑组织Nogo-A的表达在对照组和银杏叶治疗组3d开始增高,21 d达到最高峰,对照组增高幅度最大,其平均光密度值与假手...     

Effects of adenosine receptor agents on the expression of morphine withdrawal in mice

Effects of different doses of adenosine receptor agonists and antagonists on naloxone-induced jumping and diarrhea in morphine-dependent mice were studied. The adenosine A1 receptor agonists, N6-cyclohexyladenosine (CHA: 0.1, 0.25 and 0.5 mg kg(-1)) and R-isomer of N6-phenylisopropyladenosine (R-PIA: 0.1, 0.3 and 1 mg kg(-1)), decreased jumping and diarrhea induced by naloxone in morphine-dependent mice. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX: 0.3-9 mg kg(-1)), increased jumping but decreased diarrhea. The adenosine A2 receptor agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), decreased jumping and diarrhea. However, the adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 0.5 and 1 mg kg(-1)), did not elicit any response in this respect. DPCPX (0.3 and 3 mg kg(-1)), decreased the inhibition of jumping and diarrhea induced by CHA (0.5 mg kg(-1)), while DMPX (0.5 and 1 mg kg(-1)), decreased the inhibition of diarrhea induced by CPCA (0.1 mg kg(-1)). It is concluded that jumping induced by naloxone in morphine-dependent mice may be modified by the adenosine A receptor mechanism(s) and diarrhea induced by the opioid receptor antagonist could be mediated by the adenosine A1 and A2 receptors.     

Differential effect of NMDA receptor antagonist in the nucleus accumbens on reconsolidation of morphine -related positive and aversive memory in rats

Dysfunctional reconsolidation processes may help drug memories resist extinction and contribute to high rate of relapse. Reconsolidation of drug memory is mainly affected by the appetitive and aversive emotional experiences associated with an addictive drug. The nucleus accumbens has been shown to mediate the reconsolidation of positive emotional addictive memory, but its role in negative emotional addictive memory remains elusive. In the present study, we used morphine-induced CPP (m-CPP) and morphine-naloxone induced conditioned place aversion (m-CPA) to investigate the role of N-methyl-d-aspartate (NMDA) receptors within the nucleus accumbens on reconsolidation of emotional drug memory. Here we demonstrate that infusion of the NMDA receptor antagonist, d-(-)-2 amino-5-phosphonopentanoic acid ((D)-APV), into the nucleus accumbens before memory reactivation disrupts the reconsolidation of m-CPP, but does not affect m-CPA. The effect on m-CPP reconsolidation depended on memory reactivation: (D)-APV infusion had no effect in the absence of reactivation. The findings show that the glutamatergic NMDA receptor in nucleus accumbens mechanisms involved in reconsolidating aversive and positive morphine-associated memories can be dissociated.     

Nogo-A蛋白及Nogo受体抑制剂防治中枢神经系统疾病的研究进展

缺氧缺血、感染、脱髓鞘等多种因素均可造成儿童中枢神经系统损害,严重威胁儿童生命和健康,死亡率和致残率高。传统的观点认为中枢神经损伤后不能再生。研究证实,阻止中枢神经损伤后再生的重要原因是中枢神经的内环境中存在抑制神经再生的因子。其中,Nogo-A蛋白及其受体发挥着重要作用,近年来关于Nogo-A、Nogo受体及其抑制剂在中枢神经系统损伤和再生方面取得不少研究进展,现加以总结。     

Effects of dextromethorphan on dopamine release in the nucleus accumbens: Interactions with morphine

Dextromethorphan has been reported to decrease the self-administration of several drugs of abuse, including morphine, methamphetamine, cocaine, and nicotine. Most drugs of abuse increase extracellular levels of dopamine (DA) in the shell of the nucleus accumbens. The effects of dextromethorphan on DA release in the nucleus accumbens of nai;ve rats and of rats treated acutely and chronically with morphine were studied using in vivo microdialysis. DA dialysate levels were evaluated by high-performance liquid chromatography with electrochemical detection. Acute morphine (5 mg/kg i.p.) treatment increased the levels of DA in the nucleus accumbens to approximately 175% of basal levels. Chronic morphine (20 mg/kg i.p. daily for 5 days) increased DA release in the nucleus accumbens to 250% of basal levels. Acute treatment with dextromethorphan (20 or 30 mg/kg s.c.) alone did not alter nucleus accumbens DA levels. Pretreatment with dextromethorphan (20 mg/kg s.c., 20 min prior) potentiated the effects of acute morphine, while attenuating the effects of chronic morphine on nucleus accumbens DA levels. These results with dextromethorphan suggest that the mechanism mediating the effects of dextromethorphan on drug self-administration involves modulation of the dopaminergic mesolimbic pathway.     

The role of nitric oxide within the nucleus accumbens on the acquisition and expression of morphine-induced place preference in morphine sensitized rats

In the present study, the effects of intra-accumbal administration of L-arginine, a nitric oxide precursor, and N(G)-nitro-L-arginine methyl-ester (L-NAME), a nitric oxide synthase inhibitor, on the acquisition and expression of morphine-induced place conditioning in morphine-sensitized rats were studied. Subcutaneous (s.c.) administration of morphine (2.5, 5 and 7.5 mg/kg) induced conditioned place preference. Repeated pretreatment of morphine (5 mg/kg, i.p.) followed by 5 days without drug treatment, increased conditioning response induced by morphine (0.25, 0.5 and 0.75 mg/kg). Intra-accumbal (intra-nucleus accumbens; 1 microg/rat) administration of L-arginine (0.3, 1 and 3 microg/rat) significantly increased or reduced the acquisition of morphine place conditioning in non-sensitized and sensitized rats respectively. However, the drug reduced expression of place conditioning by morphine in sensitized animals. Intra-nucleus accumbens injections of L-NAME (0.3, 1 and 3 microg/rat) reduced the acquisition and expression of morphine place conditioning in the sensitized animals. The results indicate that nitric oxide (NO) within the nucleus accumbens is involved in the acquisition and expression of morphine place conditioning in morphine-sensitized rats.     

Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens on rat intravenous morphine self-administration

The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous morphine self-administration were assessed. Pairs of male rat littermates were implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and then allowed to intravenously self-administer with continuous access. When stable baselines of drug intake were obtained (2-3 weeks), one of each pair received bilateral microinjections of vehicle and the other 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection and the animals were again allowed to self-administer while drug intake was monitored for thirteen days. The littermate pairs were then sacrificed by immersion in liquid nitrogen, the brains removed at -20 degrees C and frozen sections of the cannulae tract taken for histological assessment. The nucleus accumbens, anterior caudate nucleus and pyriform cortex were removed at -20 degrees C and biogenic monoamine content determined. The 5,7-DHT lesions resulted in a significant increase in drug intake and significantly decreased the content of serotonin (5-HT) and 5-hydroxyindoleacetic acid in the nucleus accumbens (-49% and -30%, respectively) and 5-HT in the anterior caudate nucleus (-14%) and pyriform cortex (-17%). Dose-effect relationships were assessed in four additional animals before and after similar bilateral 5,7-DHT lesions.(ABSTRACT TRUNCATED AT 250 WORDS)