天麻素干预后甲基苯丙胺依赖大鼠相关脑区五羟色胺受体5HT1A、5HT2A的表达
发布时间：2018-11-11 12:01
【摘要】：[目的]建立甲基苯丙胺(methamphetamine,MA)依赖大鼠模型,使用天麻素进行干预,观察甲基苯丙胺依赖大鼠相关六个脑区(伏隔核、纹状体、海马、额叶皮质、黑质、中脑腹侧被盖区)天麻素干预前后5-羟色胺受体-1(5-HT 1A)、5-羟色胺受体-2(5-HT2A)的表达变化,探讨甲基苯丙胺对大鼠的神经毒性作用及天麻素是否对甲基苯丙胺依赖大鼠中枢神经系统损害有保护或治疗作用。[方法]SD大鼠80只,随机分为10组,每组8只。分为六周组和八周组。其中每组又分为五个亚组。六周组:生理盐水组(NS)、两周NS+四周天麻素10mg组、两周甲基苯丙胺(MA)+四周NS组、两周MA+四周天麻素10mg组、两周MA+四周天麻素20mg组。八周组:生理盐水组、四周NS+四周天麻素10mg组、四周MA+四周NS组、四周MA+四周天麻素10mg组、四周MA+四周天麻素20mg组。通过腹腔注射甲基苯丙胺,条件性位置偏爱实验(CPP)和刻板行为评分观察行为学变化,建立甲基苯丙胺依赖大鼠模型。确认大鼠产生甲基苯丙胺依赖后,建成不同时间段的依赖模型,并用天麻素干预。应用免疫荧光、蛋白免疫印迹技术和实时定量PCR技术检测大鼠不同脑区五羟色胺受体5-HT 1A和5-HT 2A的表达变化。[结果]1.与空白对照组相比,MA依赖组的条件性位置偏爱结果有显著性差异(P0.05),成功建立了甲基苯丙胺依赖模型。2.5-HT 1A和5-HT 2A在额叶皮质、海马、纹状体、伏隔核主要在细胞核内表达,而中脑腹侧被盖和黑质在胞膜和胞浆表达。3.qRT-PCR和WB显示实验结果显示:在额叶皮质、纹状体、海马、中脑腹侧被盖四个脑区,MA 2W+天麻素4W(10mg)组(P0.01)和MA 2W+天麻素4W(20mg)(P0.01)组5-HT 1A表达均明显高于MA 2W+NS 4W组;MA 4W+天麻素4W(10mg)组5-HT1A表达明显高于MA2W+天麻素4W(10mg)组(P0.01)。与MA4W+NS4W组比较,MA4W+天麻素4W(20mg)组5-HT1A表达明显增高(P0.05)。其余各组相互比较,5-HT1A表达水平均没有统计学差异。在额叶皮质、纹状体、海马、中脑腹侧被盖四个脑区,MA 2W+天麻素4W(10mg)组(P0.01)和MA 2W+天麻素4W(20mg)(P0.01)组5-HT 2A表达均明显高于MA 2W+NS 4W组;MA 4W+天麻素4W(10mg)组5-HT 2A表达明显高于MA 2W+天麻素4W(10mg)组(P0.01)。与MA4W+NS4W组比较,MA4W+天麻素4W(20mg)组5-HT2A表达明显增高(P0.05)。其余各组相互比较,5-HT 2A表达水平均没有统计学差异。[结论]1.腹腔注射甲基苯丙胺,结合条件性位置偏爱实验和刻板行为评分,建立甲基苯丙胺依赖大鼠模型。2.甲基苯丙胺依赖大鼠5-HT 1A和5-HT 2A在额叶皮质、海马、中脑腹侧被盖、伏隔核、纹状体、黑质表达变化均有不同,提示5-HT1A和5-HT2A参与了甲基苯丙胺对神经系统的毒性作用;3.MA依赖大鼠的额叶皮质、纹状体、海马、中脑腹侧被盖四个脑区额5-HT 1A及5-HT 2A表达升高,20mg天麻素干预能有效降低其表达水平,提示天麻素可能成为治疗MA所致的神经毒性损害和依赖的潜在药物。
[Abstract]:[objective] to establish methamphetamine (methamphetamine,MA) dependent rat model and to observe six brain regions (nucleus accumbens, striatum, hippocampus, frontal cortex, substantia nigra) associated with methamphetamine dependent rats. The expression of 5-hydroxytryptamine receptor-1 (5-HT 1A) and serotonin receptor 2 (5-HT2A) in ventral tegmental area of the mesencephalon before and after the intervention of Gastrodin. To investigate the neurotoxic effect of methamphetamine on rats and whether Gastrodin has protective or therapeutic effects on central nervous system damage in methamphetamine dependent rats. [methods] 80 SD rats were randomly divided into 10 groups with 8 rats in each group. They were divided into six week group and eight week group. Each group was divided into five subgroups. Six weeks group: normal saline group, (NS), group, NS 4 weeks 10mg group, 2 week NS group, 2 week MA 4 weeks Gastrodin 10mg group, 2 week MA 4 weeks Gastrodin 20mg group, 2 weeks methamphetamine (MA) 4 weeks NS group, 2 week MA 4 weeks Gastrodin 10mg group, 2 weeks MA 4 weeks Gastrodin 20mg group. Eight weeks group: normal saline group, four weeks NS four weeks Gastrodin 10mg group, four MA four weeks NS group, four weeks MA four weeks Gastrodin 10mg group, four weeks MA four weeks Gastrodin 20mg group. A model of methamphetamine dependent rats was established by intraperitoneal injection of methamphetamine, conditioned place preference experiment (CPP) and stereotypical behavior score. After methamphetamine dependence was produced in rats, dependence models of different time periods were established and treated with Gastrodin. The expression of serotonin receptor 5-HT 1A and 5-HT 2A in different brain regions of rats was detected by immunofluorescence, Western blot and real-time quantitative PCR. [result] 1. Compared with the control group, the results of conditioned place preference in MA dependent group were significantly different (P0.05). The methamphetamine dependent model was successfully established. 2.5-HT 1A and 5-HT 2A were found in frontal cortex, hippocampus and striatum. The nucleus accumbens were mainly expressed in the nucleus, while ventral tegmental and substantia nigra were expressed in the cell membrane and cytoplasm. The results of 3.qRT-PCR and WB showed that there were four brain regions in the frontal cortex, striatum, hippocampus, ventral tegmentum of the midbrain. The expression of 5-HT 1A in MA 2W Gastrodin 4W (10mg) group and MA 2W Gastrodin 4W (20mg) group was significantly higher than that in MA 2W NS 4W group. The expression of 5-HT1A in MA 4W Gastrodin 4W (10mg) group was significantly higher than that in MA2W Gastrodin 4W (10mg) group (P0.01). Compared with MA4W NS4W group, the 5-HT1A expression of MA4W Gastrodin 4 W (20mg) group was significantly higher than that of MA4W Gastrodin 4 W (20mg) group (P 0.05). There was no significant difference in 5-HT1A expression among the other groups. The expression of 5-HT 2A in frontal cortex, striatum, hippocampus, ventral tegmental tegmentum, MA 2W Gastrodin 4W (10mg) group and MA 2W Gastrodin 4W (20mg) group was significantly higher than MA 2W NS 4W group. The expression of 5-HT 2A in MA 4W Gastrodin 4W (10mg) group was significantly higher than that in MA 2W Gastrodin 4W (10mg) group (P0.01). Compared with MA4W NS4W group, the 5-HT2A expression of MA4W Gastrodin 4 W (20mg) group was significantly higher than that of MA4W Gastrodin 4 W (20mg) group (P 0.05). There was no significant difference in the expression of 5-HT 2A among the other groups. [conclusion] 1. The methamphetamine dependent rat model was established by intraperitoneal injection of methamphetamine combined with conditional place preference test and stereotypical behavior score. 2. The expression changes of 5-HT 1A and 5-HT 2A in frontal cortex, hippocampus, ventral tegmentum, nucleus accumbens, striatum and substantia nigra were different in methamphetamine dependent rats. It is suggested that 5-HT1A and 5-HT2A are involved in the toxic effect of methamphetamine on nervous system. The expression of 5-HT 1A and 5-HT 2A in frontal cortex, striatum, hippocampus and ventral tegmental area of 3.MA dependent rats were increased, and 20mg Gastrodin could effectively decrease the expression level. It suggests that Gastrodin may be a potential drug in the treatment of neurotoxic damage and dependence caused by MA.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.64
[Abstract]:[objective] to establish methamphetamine (methamphetamine,MA) dependent rat model and to observe six brain regions (nucleus accumbens, striatum, hippocampus, frontal cortex, substantia nigra) associated with methamphetamine dependent rats. The expression of 5-hydroxytryptamine receptor-1 (5-HT 1A) and serotonin receptor 2 (5-HT2A) in ventral tegmental area of the mesencephalon before and after the intervention of Gastrodin. To investigate the neurotoxic effect of methamphetamine on rats and whether Gastrodin has protective or therapeutic effects on central nervous system damage in methamphetamine dependent rats. [methods] 80 SD rats were randomly divided into 10 groups with 8 rats in each group. They were divided into six week group and eight week group. Each group was divided into five subgroups. Six weeks group: normal saline group, (NS), group, NS 4 weeks 10mg group, 2 week NS group, 2 week MA 4 weeks Gastrodin 10mg group, 2 week MA 4 weeks Gastrodin 20mg group, 2 weeks methamphetamine (MA) 4 weeks NS group, 2 week MA 4 weeks Gastrodin 10mg group, 2 weeks MA 4 weeks Gastrodin 20mg group. Eight weeks group: normal saline group, four weeks NS four weeks Gastrodin 10mg group, four MA four weeks NS group, four weeks MA four weeks Gastrodin 10mg group, four weeks MA four weeks Gastrodin 20mg group. A model of methamphetamine dependent rats was established by intraperitoneal injection of methamphetamine, conditioned place preference experiment (CPP) and stereotypical behavior score. After methamphetamine dependence was produced in rats, dependence models of different time periods were established and treated with Gastrodin. The expression of serotonin receptor 5-HT 1A and 5-HT 2A in different brain regions of rats was detected by immunofluorescence, Western blot and real-time quantitative PCR. [result] 1. Compared with the control group, the results of conditioned place preference in MA dependent group were significantly different (P0.05). The methamphetamine dependent model was successfully established. 2.5-HT 1A and 5-HT 2A were found in frontal cortex, hippocampus and striatum. The nucleus accumbens were mainly expressed in the nucleus, while ventral tegmental and substantia nigra were expressed in the cell membrane and cytoplasm. The results of 3.qRT-PCR and WB showed that there were four brain regions in the frontal cortex, striatum, hippocampus, ventral tegmentum of the midbrain. The expression of 5-HT 1A in MA 2W Gastrodin 4W (10mg) group and MA 2W Gastrodin 4W (20mg) group was significantly higher than that in MA 2W NS 4W group. The expression of 5-HT1A in MA 4W Gastrodin 4W (10mg) group was significantly higher than that in MA2W Gastrodin 4W (10mg) group (P0.01). Compared with MA4W NS4W group, the 5-HT1A expression of MA4W Gastrodin 4 W (20mg) group was significantly higher than that of MA4W Gastrodin 4 W (20mg) group (P 0.05). There was no significant difference in 5-HT1A expression among the other groups. The expression of 5-HT 2A in frontal cortex, striatum, hippocampus, ventral tegmental tegmentum, MA 2W Gastrodin 4W (10mg) group and MA 2W Gastrodin 4W (20mg) group was significantly higher than MA 2W NS 4W group. The expression of 5-HT 2A in MA 4W Gastrodin 4W (10mg) group was significantly higher than that in MA 2W Gastrodin 4W (10mg) group (P0.01). Compared with MA4W NS4W group, the 5-HT2A expression of MA4W Gastrodin 4 W (20mg) group was significantly higher than that of MA4W Gastrodin 4 W (20mg) group (P 0.05). There was no significant difference in the expression of 5-HT 2A among the other groups. [conclusion] 1. The methamphetamine dependent rat model was established by intraperitoneal injection of methamphetamine combined with conditional place preference test and stereotypical behavior score. 2. The expression changes of 5-HT 1A and 5-HT 2A in frontal cortex, hippocampus, ventral tegmentum, nucleus accumbens, striatum and substantia nigra were different in methamphetamine dependent rats. It is suggested that 5-HT1A and 5-HT2A are involved in the toxic effect of methamphetamine on nervous system. The expression of 5-HT 1A and 5-HT 2A in frontal cortex, striatum, hippocampus and ventral tegmental area of 3.MA dependent rats were increased, and 20mg Gastrodin could effectively decrease the expression level. It suggests that Gastrodin may be a potential drug in the treatment of neurotoxic damage and dependence caused by MA.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.64
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