本文選題：苯丙胺 + 紋狀體　； 參考：《暨南大學(xué)》2014年碩士論文

【摘要】：目的 探討mTORC2通路在苯丙胺致大鼠紋狀體損傷的變化。 方法 通過給予SD大鼠腹腔注射苯丙胺（2.5mg/kg/d）建立動(dòng)物模型，將SD大鼠隨機(jī)分為空白組、生理鹽水組與苯丙胺處理組，苯丙胺處理組又根據(jù)給藥與取材時(shí)間的不同隨機(jī)分為苯丙胺1h、1d、7d和14d組（空白組未給予任何處理；生理鹽水組注射等量生理鹽水；苯丙胺1h組給予苯丙胺注射1次，在給藥后1h取材；苯丙胺1d組、7d組和14d組分別給藥1次、7次、14次，每天1次，并于末次給藥后24h內(nèi)取材；而空白組、生理鹽水組與苯丙胺14d組一同取材）。采用Open field方法測(cè)試SD大鼠在給藥前、后的自主行為活動(dòng)，用刻板行為評(píng)分方法(GHF-Dodd法)評(píng)價(jià)大鼠的刻板行為。用透射電鏡觀察大鼠紋狀體部位神經(jīng)元超微結(jié)構(gòu)的損傷狀況；Western blot方法檢測(cè)mTORC2信號(hào)在紋狀體的表達(dá)；免疫組化方法定位磷酸化的mTORC2在紋狀體神經(jīng)元的表達(dá)分布。 結(jié)果 行為學(xué)結(jié)果自主行為活動(dòng)測(cè)試發(fā)現(xiàn)給予苯丙胺處理后，苯丙胺1d、7d、14d組自主活動(dòng)的總距離、速度、運(yùn)動(dòng)時(shí)間與空白組比較增加，具有顯著性差異（p0.01）。此外，刻板行為評(píng)分結(jié)果顯示，苯丙胺7d、14d組與空白組比較刻板行為評(píng)分增加，具有顯著性差異（p0.01）。 透射電鏡結(jié)果透射電鏡觀察發(fā)現(xiàn)紋狀體空白組細(xì)胞結(jié)構(gòu)清晰，胞核大，線粒體多呈圓形或橢圓形，，線粒體膜結(jié)構(gòu)清晰、嵴排列整齊；神經(jīng)纖維結(jié)構(gòu)清楚、完整。生理鹽水組、苯丙胺1d組與空白組比較細(xì)胞結(jié)構(gòu)未見明顯差異。而苯丙胺14d組紋狀體細(xì)胞結(jié)構(gòu)模糊，核固縮，線粒體腫脹變形、嵴排列紊亂、斷裂；紋狀體神經(jīng)纖維結(jié)構(gòu)扭曲變形、甚至可見斷裂。 Western blot結(jié)果在紋狀體部位，P-rictor(S1219）在苯丙胺1d組（p=0.013）、7d組（p=0.021）、14d組（p=0.031）與空白組比較表達(dá)減少有統(tǒng)計(jì)學(xué)差異；P-AKT(T308)在苯丙胺14d組與空白組比較表達(dá)減少，p=0.000，具有顯著性差異。 免疫組化結(jié)果在紋狀體部位，P-rictor(S1219）免疫陽(yáng)性細(xì)胞在紋狀體尾殼核（CPU）和腹側(cè)蒼白球（LGP）都有分布；陽(yáng)性產(chǎn)物主要分布在胞漿中，胞核淡染。P-rictor(S1219）陽(yáng)性細(xì)胞數(shù)在苯丙胺7d組（p=0.006）、14d組(p=0.006)與空白組比較表達(dá)減少，具有顯著性差異，與Western blot結(jié)果相一致。 結(jié)論 苯丙胺對(duì)紋狀體的損傷機(jī)制可能與抑制mTORC2/AKT信號(hào)的表達(dá)有關(guān)。
[Abstract]:Purpose To investigate the changes of mTORC2 pathway in rat striatum injury induced by amphetamine. Method Sprague-Dawley rats were randomly divided into blank group, saline group and amphetamine treated group by intraperitoneal injection of 2.5 mg / kg 路kg / d of amphetamine. The amphetamine treatment group was also randomly divided into two groups according to the time of administration and taking materials. The control group was given no treatment, the saline group was injected with the same amount of normal saline, and the amphetamine 1h group was given the amphetamine injection once. The samples were obtained at 1 hour after administration of amphetamine, 14 times a day, once a day, and within 24 hours after the last administration in the 1-day group and 14d group, respectively, while in the blank group, the samples were taken together with the 14d group of amphetamine. Open field method was used to measure the autonomous behavior of SD rats before and after administration, and the stereotypical behavior was evaluated by GHF-Dodd method. The ultrastructure of neurons in rat striatum was observed by transmission electron microscope. The expression of mTORC2 signal in striatum was detected by Western blot, and the expression distribution of phosphorylated mTORC2 in striatum neurons was determined by immunohistochemical method. Result The results of behavioral test showed that the total distance, speed and exercise time of the group treated with amphetamine were significantly higher than those of the blank group (p 0.01). The total distance, speed and exercise time of the group treated with amphetamine were significantly higher than those of the blank group (P < 0.01). In addition, the scores of stereotype behavior in the amphetamine group on day 14 were significantly higher than those in the control group (p 0.01). The results of transmission electron microscope showed that the structure of striatum blank group was clear, the nucleus was large, the mitochondria were round or ellipse, the membrane structure of mitochondria was clear, the ridge was arranged neatly, and the structure of nerve fibers was clear and complete. There was no significant difference in cell structure between the saline group and the 1 d group compared with the blank group. In 14 d group, the structure of striatum cells was blurred, nucleus constricted, mitochondria swollen and deformed, ridge arranged disordered and broken, and striatum nerve fiber structure distorted and even broken. Western blot results: the expression of P-rictorus S1219 in the striatum was significantly lower than that in the control group (P 0.000). The expression of P-AKTT in the control group was significantly lower than that in the control group (P 0.000) compared with the control group on the 1st day, the expression of P-AKT was significantly lower in the control group than that in the control group on the 1st day, and the expression of P-AKT was significantly lower than that in the control group on the 1st day group (P 0.013) and in the control group on the 7th day (P 0.031), there was a significant difference between the two groups. The immunoreactive cells of P-rictorus S1219 in the striatum were distributed in the caudate putamen (CPU) and the ventral globus pallidus (LGP), and the positive products were mainly distributed in the cytoplasm. The expression of P0. 006 in the P0. 006 / 14d group was significantly lower than that in the control group, which was consistent with the results of Western blot. The number of the cells in the nucleus of the control group was significantly lower than that of the control group (P < 0. 006), and the results were consistent with those of the control group (P < 0. 006), which was consistent with the results of Western blot. Conclusion The mechanism of striatum injury induced by amphetamine may be related to the inhibition of mTORC2/AKT signal expression.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965

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