甲基苯丙胺中毒mG1uR5的表达（英文）

目的：研究代谢性谷氨酸受体5（mG1uR5）在甲基苯丙胺中毒的损伤机制中的作用。方法：设立实验组,对照组。实验组分别给予20 mg/kg,10 mg/kg腹腔注射MA;对照组分别给予同剂量的生理盐水。末次注射后24 h内腹腔注射戊巴比妥钠麻醉大鼠后用4%多聚甲醛灌注、取脑后行代谢性谷氨酸受体5的免疫组织化学染色,观察并计数mG1uR5在不同脑区的表达。结果：实验组mG1uR5在大脑纹状体、海马的表达较对照组显著增强,差异有显著性（P〈0.05）,并呈剂量依赖性。结论：mG1uR5参与了甲基苯丙胺中毒的损伤机制。     

甲基苯丙胺中毒大鼠相关脑区Caspase-3和Bcl-2表达的研究

目的：研究凋亡相关因子Caspase-3和Bcl-2在甲基苯丙胺神经毒性机制中所发挥的作用。方法：40只健康雄性SD大鼠随机分为对照组（n=10）和实验组（又分为3个亚组,分别为注射1天后、4天后、7天后,n=10）。实验组给予20mg/kg的甲基苯丙胺腹腔注射,对照组给予相同剂量的生理盐水注射。用免疫组化检测中毒大鼠相关脑区Caspase-3和Bcl-2的表达,用图像分析技术对检测结果进行分析。结果：Caspase-3在中毒大鼠不同脑区表达逐渐增加并可见明显的阳性信号;Bcl-2在中毒大鼠不同脑区表达逐渐减弱。结论：凋亡相关因子Caspase-3和Bcl-2参与了甲基苯丙胺神经毒性机制。     

甲基苯丙胺中毒大鼠相关脑区Caspase-3 和Bcl-2 表达的研究

目的:研究凋亡相关因子Caspase-3和Bcl-2在甲基苯丙胺神经毒性机制中所发挥的作用。方法:40只健康雄性SD大鼠随机分为对照组(n=10)和实验组(又分为3个亚组,分别为注射1天后、4天后、7天后,n=10)。实验组给予20mg/kg的甲基苯丙胺腹腔注射,对照组给予相同剂量的生理盐水注射。用免疫组化检测中毒大鼠相关脑区Caspase-3和Bcl-2的表达,用图像分析技术对检测结果进行分析。结果:Caspase-3在中毒大鼠不同脑区表达逐渐增加并可见明显的阳性信号;Bcl-2在中毒大鼠不同脑区表达逐渐减弱。结论:凋亡相关因子Caspase-3和Bcl-2参与了甲基苯丙胺神经毒性机制。     

甲基苯丙胺中毒小鼠脑组织神经元超微结构变化的研究

目的：通过观察甲基苯丙胺中毒后小鼠脑组织超微结构的改变,探讨脑组织超微结构改变与甲基苯丙胺神经毒性机制的关系。方法：将40只小鼠随机分为对照组和3组实验组（A,B,C）。A组给予MA（20mg/kg,ip,single）、B组给予MA（20mg/kg,8am,8pm,ip×2d）、C组给予MA（20mg/kg,8am,8pm,ip×4d）,对照组给予等量生理盐水。用电镜观察前额叶皮质、海马、纹状体三个部位组织神经元胞体超微结构改变,并与空白对照组比较,结果进行统计学处理。结果：给予MA后,小鼠各脑区神经元胞体出现神经元固缩、变性、凋亡、坏死等超微病变。结论：MA可诱导神经细胞发生神经元固缩、变性、凋亡、坏死等超微病变,其变化程度随时间和药物蓄积有逐渐增加的趋势。     

甲基苯丙胺中毒小鼠脑组织神经元 超微结构变化的研究

目的:通过观察甲基苯丙胺中毒后小鼠脑组织超微结构的改变,探讨脑组织超微结构改变与甲基苯丙胺神经毒性机制的关系。方法:将40只小鼠随机分为对照组和3组实验组(A,B,C)。A组给予MA(20mg/kg,ip,single)、B组给予MA(20mg/kg,8am,8pm,ip×2d)、C组给予MA(20mg/kg,8am,8pm,ip×4d),对照组给予等量生理盐水。用电镜观察前额叶皮质、海马、纹状体三个部位组织神经元胞体超微结构改变,并与空白对照组比较,结果进行统计学处理。结果:给予MA后,小鼠各脑区神经元胞体出现神经元固缩、变性、凋亡、坏死等超微病变。结论:MA可诱导神经细胞发生神经元固缩、变性、凋亡、坏死等超微病变,其变化程度随时间和药物蓄积有逐渐增加的趋势。     

甲基苯丙胺对心血管系统的影响及其机制的研究进展

甲基苯胺(Methamphetamine,MA)不但影响神经系统,而且对心血管系统也会产生影响.急性MA中毒可以引起心动过速、心律不齐、心肌缺血及高血压,最终导致心脏的损伤;慢性MA中毒可以引起心肌炎性细胞浸润、心肌肥厚、心肌纤维化甚至心脏破裂.本文就MA滥用对心血管系统的影响及其机制的研究进展进行综述.     

甲基苯丙胺中毒大鼠相关脑区多巴胺能神经毒性研究

目的：探讨MA中毒多巴胺能神经毒性的损伤机制。方法：将Wistar大鼠40只,随机分成对照组10只和实验组30只（实验组分成三个亚组,分为末次给药后1天组、4天组和7天组,n=10）。实验组给予20mg/kg的MA腹腔注射,对照组给予同样剂量的生理盐水,每天注射一次,注射时间为20：00,连续注射4天。分别于末次给药后1天,7天,14天处死实验大鼠,用免疫组织化学染色法（S-P法）和荧光分光光度计法检测大鼠中脑黑质致密区（SNC）、中脑腹侧被盖区（VTA）、前额叶皮质（PFC）以及纹状体（CPu）四个脑区的多巴胺神经元细胞的形态和数量的变化,对神经纤维进行灰度值分析。结果：1、黑质致密区和腹侧被盖区TH阳性细胞图像分析结果与细胞计数分析结果一致：与对照组相比,各实验组TH免疫反应阳性降低,差异具显著性（P〈0.05）,d1组开始降低（P〈0.05）,d7组达到低谷（P〈0.01）,d14天组黑质致密区和腹侧被盖区TH免疫反应阳性有不同程度的恢复（P〈0.05）。2、纹状体和前额叶皮质TH阳性纤维图像定量分析结果：各实验组TH免疫反应阳性均减低（P〈0.05）,d7组阳性反应最弱（P〈0.01）,d14组仍未恢复（P〈0.05）。3、黑质致密区、腹侧被盖区、纹状体及前额叶皮质荧光分光光度计检测DA递质含量结果：与上述免疫组化结果基本一致。结论：1、大鼠各脑区TH阳性表达和DA含量,均出现不同程度的减低。2、MA中毒大鼠各脑区DA递质含量的变化与TH的变化结果基本一致。     

甲基苯丙胺中毒大鼠相关脑区多巴胺能神经毒性研究

目的:探讨MA中毒多巴胺能神经毒性的损伤机制。方法:将Wistar大鼠40只,随机分成对照组10只和实验组30只(实验组分成三个亚组,分为末次给药后1天组、4天组和7天组,n=10)。实验组给予20mg/kg的MA腹腔注射,对照组给予同样剂量的生理盐水,每天注射一次,注射时间为20:00,连续注射4天。分别于末次给药后1天,7天,14天处死实验大鼠,用免疫组织化学染色法(S-P法)和荧光分光光度计法检测大鼠中脑黑质致密区(SNC)、中脑腹侧被盖区(VTA)、前额叶皮质(PFC)以及纹状体(CPu)四个脑区的多巴胺神经元细胞的形态和数量的变化,对神经纤维进行灰度值分析。结果:1、黑质致密区和腹侧被盖区TH阳性细胞图像分析结果与细胞计数分析结果一致:与对照组相比,各实验组TH免疫反应阳性降低,差异具显著性(P<0.05),d1组开始降低(P<0.05),d7组达到低谷(P<0.01),d14天组黑质致密区和腹侧被盖区TH免疫反应阳性有不同程度的恢复(P<0.05)。2、纹状体和前额叶皮质TH阳性纤维图像定量分析结果:各实验组TH免疫反应阳性均减低(P<0.05),d7组阳性反应最弱(P<0.01),d14组仍未恢复(P<0.05)。3、黑质致密区、腹侧被盖区、纹状体及前额叶皮质荧光分光光度计检测DA递质含量结果:与上述免疫组化结果基本一致。结论:1、大鼠各脑区TH阳性表达和DA含量,均出现不同程度的减低。2、MA中毒大鼠各脑区DA递质含量的变化与TH的变化结果基本一致。     

甲基苯丙胺神经毒性及防治的研究进展

甲基苯丙胺近年来在国际上迅速泛滥,作为一类精神刺激药物,世界范围内对其神经毒性的研究一直是热点问题.随着分子生物学及功能影像学等各种技术的快速发展,甲基苯丙胺的神经毒性机制研究日益深入,但是其防治仍然有待进一步研究.本文参考了近年来发表的国内外文献27篇,对其神经毒性及防治作一综述.     

以耐草甘膦2mG2-epsps基因为选择标记的玉米转化体系的建立

转化细胞的筛选和再生是植物遗传转化体系中重要的组成部分,筛选剂的选择和筛选压力的高低直接影响着外源基因的转化率。以草甘膦异丙胺盐为筛选剂,通过比较在不同的草甘膦浓度及筛选时间的条件下,玉米愈伤组织生长和分化情况,发现经1mM的草甘膦异丙胺盐筛选15d后玉米愈伤组织分化受到明显抑制,故以此作为玉米遗传转化实验中的筛选压力。通过基因枪轰击,将构建好的pMAGUHM载体（其上携带有抗草甘膦基因2mG2-epsps基因）转化到玉米愈伤组织,利用草甘膦筛选得到耐草甘膦植株80株,其中PCR检测阳性植株为36株,转化率为45％。     

甲基苯丙胺中毒大鼠纹状体COX-2、PGE2、EP2 受体及小胶质细胞 表达的研究

目的:通过研究COX-2、PGE2、EP2受体及小胶质细胞在甲基苯丙胺中毒大鼠纹状体内的表达变化探讨甲基苯丙胺中毒大鼠纹状体中COX-2/PGE2系统与小胶质细胞活化之间的关系。方法:将40只健康成年雄性SD大鼠,随机分成对照组10只和实验组30只(实验组分成三个亚组,分为末次给药后1天组、2天组和3天组,n=10)。实验组给予10mg/kg的MA腹腔注射,对照组给予同样剂量的生理盐水,每天注射两次,注射时间为8:00、20:00,连续注射4天。分别于末次给药后的第1天、第2天、第3天处杀。用免疫组化技术对中毒大鼠纹状体(CPU)中COX-2、EP2受体及Iba1(钙离子接头蛋白,小胶质细胞内一种特异性标记物)的表达进行检测,并进行图像分析。另外,取大鼠的纹状体运用酶联免疫法检测PGE2的含量。结果:COX-2、PGE2、EP2受体及小胶质细胞在各组均有表达。与对照组相比,实验组中:COX-2、PGE2、EP2受体的1天组表达均不同程度下降;2天组中COX-2表达水平大幅度上升,PGE2、EP2受体表达仍低于正常水平;3天组COX-2表达水平继续升高,而PGE2、EP2受体表达趋于正常组水平。而小胶质细胞表达水平则是三个实验组均高于正常组,且3天组高于2天组,2天组高于1天组。对照组与实验组有显著性差异(P<0.05)。结论:COX-2/PGE2系统与甲基苯丙胺中毒大鼠纹状体内小胶质细胞活化无明显相关性;COX-2与甲基苯丙胺的神经毒性有关。     

Effects of Glutamate Antagonists on Methamphetamine and 3,4-Methylenedioxymethamphetamine-Induced Striatal Dopamine Release In Vivo

Abstract: Several amphetamine analogues are reported to increase striatal glutamate efflux in vivo, whereas other data indicate that glutamate is capable of stimulating the efflux of dopamine (DA) in the striatum via a glutamate receptor-dependent mechanism. Based on these findings, it has been proposed that the ability of glutamate receptor-blocking drugs to antagonize the effects of amphetamine may be explained by their capacity to inhibit DA release induced by glutamate. To examine this possibility further, we investigated in vivo the ability of glutamate antagonists to inhibit DA release induced by either methamphetamine (METH) or 3,4-methylenedioxymethamphetamine (MDMA). Both METH and MDMA increased DA efflux in the rat striatum and, in animals killed 1 week later, induced persistent depletions of DA and serotonin in tissue. Pretreatment with MK-801 or CGS 19755 blocked the neurotoxic effects of METH and MDMA but, did not significantly alter striatal DA efflux induced by either stimulant. Infusion of 6-cyano-7-nitroquinoxaline-2,3-dione into the striatum likewise did not alter METH-induced DA overflow, and none of the glutamatergic antagonists affected the basal release of DA when given alone. The findings suggest that the neuroprotective effects of NMDA antagonists do not involve an inhibition of DA release, nor do the data support the proposal that glutamate tonically stimulates striatal DA efflux in vivo. Whether phasic increases in glutamate content might stimulate DA release, however, remains to be determined.     

5-Hydroxy-3-Ethylamino-2-Oxindole Is Not Formed in Rat Brain Following a Neurotoxic Dose of Methamphetamine: Evidence that Methamphetamine Does Not Induce the Hydroxyl Radical-Mediated Oxidation of Serotonin

Abstract: Oxygen radicals have been implicated in the neurodegenerative and other neurobiological effects evoked by methamphetamine (MA) in the brain. It has been reported that shortly after a single large subcutaneous dose of MA to the rat, the serotonergic neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) is formed in the cortex and hippocampus. This somewhat controversial finding suggests that MA potentiates formation of the hydroxyl radical (HO^?) that oxidizes 5-hydroxytryptamine (5-HT) to 5,6-DHT, which, in turn, mediates the degeneration of serotonergic terminals. A major and more stable product of the in vitro HO^?-mediated oxidation of 5-HT is 5-hydroxy-3-ethylamino-2-oxindole (5-HEO). In this investigation, a method based on HPLC with electrochemical detection (HPLC-EC) has been developed that permits measurement of very low levels of 5-HEO in rat brain tissue in the presence of biogenic amine neurotransmitters/metabolites. After intracerebroventricular administration into rat brain, 5-HEO is transformed into a single major, but unknown, metabolite that can be detected by HPLC-EC. One hour after administration of MA (100 mg/kg s.c.) to the rat, massive decrements of 5-HT were observed in all regions of the brain examined (cortex, hippocampus, medulla and pons, midbrain, and striatum). However, 5-HEO, its unidentified metabolite, or 5,6-DHT were not detected as in vivo metabolites of 5-HT. MA administration, in particular to rats pretreated with pargyline, resulted in the formation of low levels of N-acetyl-5-hydroxytryptamine (NAc-5-HT) in all brain regions examined. These results suggest that MA does not potentiate the HO^?-mediated oxidation of 5-HT. Furthermore, the rapid MA-induced decrease of 5-HT might not only be related to oxidative deactivation of tryptophan hydroxylase, as demonstrated by other investigators, but also to the inhibition of tetrahydrobiopterin biosynthesis by NAc-5-HT. The massive decrements of 5-HT evoked by MA are accompanied by small or no corresponding increases in 5-hydroxyindole-3-acetic acid (5-HIAA) levels. This is due, in part, to the relatively rapid clearance of 5-HIAA from the brain and monoamine oxidase (MAO) inhibition by MA. However, the loss of 5-HT without corresponding increases in its metabolites point to other mechanisms that might deplete the neurotransmitter, such as oxidation by superoxide radical anion (O₂^??), a reaction that in vitro does not generate 5-HEO or 5,6-DHT but rather another putative neurotoxin, tryptamine-4,5-dione. One hour after administration, MA evokes large depletions of norepinephrine (NE) throughout the brain but somewhat smaller decrements of dopamine (DA) that are restricted to the nigrostriatal pathway. Furthermore, MA evokes a major shift in the metabolism of both NE and DA from the pathway mediated by MAO to that mediated by catechol-O-methyltransferase. The profound and widespread effects of MA on the noradrenergic system, but more anatomically localized influence on the dopaminergic system, suggests that NE in addition to DA, or unusual metabolites of these neurotransmitters, might play roles in the neurodegenerative effects evoked by this drug.