天麻素干預(yù)后甲基苯丙胺依賴大鼠相關(guān)腦區(qū)五羥色胺受體5HT1A、5HT2A的表達
發(fā)布時間：2018-11-11 12:01
【摘要】：[目的]建立甲基苯丙胺(methamphetamine,MA)依賴大鼠模型,使用天麻素進行干預(yù),觀察甲基苯丙胺依賴大鼠相關(guān)六個腦區(qū)(伏隔核、紋狀體、海馬、額葉皮質(zhì)、黑質(zhì)、中腦腹側(cè)被蓋區(qū))天麻素干預(yù)前后5-羥色胺受體-1(5-HT 1A)、5-羥色胺受體-2(5-HT2A)的表達變化,探討甲基苯丙胺對大鼠的神經(jīng)毒性作用及天麻素是否對甲基苯丙胺依賴大鼠中樞神經(jīng)系統(tǒng)損害有保護或治療作用。[方法]SD大鼠80只,隨機分為10組,每組8只。分為六周組和八周組。其中每組又分為五個亞組。六周組:生理鹽水組(NS)、兩周NS+四周天麻素10mg組、兩周甲基苯丙胺(MA)+四周NS組、兩周MA+四周天麻素10mg組、兩周MA+四周天麻素20mg組。八周組:生理鹽水組、四周NS+四周天麻素10mg組、四周MA+四周NS組、四周MA+四周天麻素10mg組、四周MA+四周天麻素20mg組。通過腹腔注射甲基苯丙胺,條件性位置偏愛實驗(CPP)和刻板行為評分觀察行為學(xué)變化,建立甲基苯丙胺依賴大鼠模型。確認大鼠產(chǎn)生甲基苯丙胺依賴后,建成不同時間段的依賴模型,并用天麻素干預(yù)。應(yīng)用免疫熒光、蛋白免疫印跡技術(shù)和實時定量PCR技術(shù)檢測大鼠不同腦區(qū)五羥色胺受體5-HT 1A和5-HT 2A的表達變化。[結(jié)果]1.與空白對照組相比,MA依賴組的條件性位置偏愛結(jié)果有顯著性差異(P0.05),成功建立了甲基苯丙胺依賴模型。2.5-HT 1A和5-HT 2A在額葉皮質(zhì)、海馬、紋狀體、伏隔核主要在細胞核內(nèi)表達,而中腦腹側(cè)被蓋和黑質(zhì)在胞膜和胞漿表達。3.qRT-PCR和WB顯示實驗結(jié)果顯示:在額葉皮質(zhì)、紋狀體、海馬、中腦腹側(cè)被蓋四個腦區(qū),MA 2W+天麻素4W(10mg)組(P0.01)和MA 2W+天麻素4W(20mg)(P0.01)組5-HT 1A表達均明顯高于MA 2W+NS 4W組;MA 4W+天麻素4W(10mg)組5-HT1A表達明顯高于MA2W+天麻素4W(10mg)組(P0.01)。與MA4W+NS4W組比較,MA4W+天麻素4W(20mg)組5-HT1A表達明顯增高(P0.05)。其余各組相互比較,5-HT1A表達水平均沒有統(tǒng)計學(xué)差異。在額葉皮質(zhì)、紋狀體、海馬、中腦腹側(cè)被蓋四個腦區(qū),MA 2W+天麻素4W(10mg)組(P0.01)和MA 2W+天麻素4W(20mg)(P0.01)組5-HT 2A表達均明顯高于MA 2W+NS 4W組;MA 4W+天麻素4W(10mg)組5-HT 2A表達明顯高于MA 2W+天麻素4W(10mg)組(P0.01)。與MA4W+NS4W組比較,MA4W+天麻素4W(20mg)組5-HT2A表達明顯增高(P0.05)。其余各組相互比較,5-HT 2A表達水平均沒有統(tǒng)計學(xué)差異。[結(jié)論]1.腹腔注射甲基苯丙胺,結(jié)合條件性位置偏愛實驗和刻板行為評分,建立甲基苯丙胺依賴大鼠模型。2.甲基苯丙胺依賴大鼠5-HT 1A和5-HT 2A在額葉皮質(zhì)、海馬、中腦腹側(cè)被蓋、伏隔核、紋狀體、黑質(zhì)表達變化均有不同,提示5-HT1A和5-HT2A參與了甲基苯丙胺對神經(jīng)系統(tǒng)的毒性作用;3.MA依賴大鼠的額葉皮質(zhì)、紋狀體、海馬、中腦腹側(cè)被蓋四個腦區(qū)額5-HT 1A及5-HT 2A表達升高,20mg天麻素干預(yù)能有效降低其表達水平,提示天麻素可能成為治療MA所致的神經(jīng)毒性損害和依賴的潛在藥物。
[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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.64
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