【摘要】： 目的： 本研究通過苯丙胺(amphetamine，AP)誘導(dǎo)的大鼠中毒模型，以其對(duì)機(jī)體肝臟的毒性損害為切入點(diǎn)，觀察在不同時(shí)間和不同劑量下，大鼠肝組織和細(xì)胞的形態(tài)學(xué)變化以及脂肪酸合成酶的活性表達(dá)，探討AP對(duì)機(jī)體臟器損害的毒理作用。 方法： SD大鼠65只，體重200±20g，隨機(jī)分成對(duì)照組(Z組，n=5)和實(shí)驗(yàn)組(A、B、C，n=20)，飼養(yǎng)及光照節(jié)律正常。A組為AP小劑量組，0.5mg／kg；B組為中劑量組，，2.5mg／kg；C組為大劑量組，5mg／kg；Z組為生理鹽水組，0.5mg／kg；給藥方式為左后肢肌肉注射。每天上午給藥一次。各組分別在用藥14d、28d和42d處死，取肝并經(jīng)石蠟包埋、切片。 1．應(yīng)用HE染色學(xué)方法，觀察大鼠肝小葉結(jié)構(gòu)及肝細(xì)胞脂肪變性、空泡樣變性、肝細(xì)胞核固縮現(xiàn)象； 2．應(yīng)用免疫組織化學(xué)方法定性和定位大鼠肝脂肪酸合成酶陽性細(xì)胞變化； 3．應(yīng)用Western Blot方法定量檢測(cè)大鼠肝脂肪酸合成酶量的變化。 結(jié)果： 1．HE染色后，光鏡下觀察到，大鼠肝內(nèi)肝竇變窄、消失，肝索解離、結(jié)構(gòu)消失；肝細(xì)胞腫脹、渾濁、細(xì)胞漿出現(xiàn)脂滴，較大的脂滴將細(xì)胞核擠壓變形；肝細(xì)胞呈現(xiàn)局部、部分或彌漫性脂肪變性；嚴(yán)重時(shí)可見肝細(xì)胞氣球樣變，邊界不清，可見核固縮。毒性損害嚴(yán)重程度隨著時(shí)間的延長和劑量的增加而加重，呈正相關(guān)性。 2．免疫組化結(jié)果顯示：大鼠肝內(nèi)脂肪酸合成酶陽性細(xì)胞胞漿呈黃染，陽性細(xì)胞數(shù)隨時(shí)間和劑量的增加而減少，呈負(fù)相關(guān)。 3．Western Blot結(jié)果表明大鼠肝內(nèi)脂肪酸合成酶的含量隨著時(shí)間和劑量的增加而減少。 結(jié)論： AP對(duì)肝臟有明顯的毒性作用，主要表現(xiàn)為肝細(xì)胞的脂肪變性和細(xì)胞水腫；同時(shí)，經(jīng)免疫組化和蛋白印跡方法證明，脂肪酸合成酶的細(xì)胞數(shù)目和含量隨著AP的使用時(shí)間和劑量的增加而減少。
[Abstract]:Objective: to study the toxic effects of amphetamine (amphetamine,AP) on the liver of rats at different time and dosage. The morphologic changes of liver tissues and cells and the expression of fatty acid synthase activity in rat liver were studied to investigate the toxicological effects of AP on organ damage. Methods: 65 SD rats, weighing 200 鹵20 g, were randomly divided into two groups: control group (group Z, n = 5) and experimental group (group A, n = 20). The feeding and illumination rhythm was normal. Group A was fed with AP (0.5 mg 路kg ~ (-1) 路kg ~ (-1) and the middle dose group was (2.5 mg 路kg ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路kg ~ (-1). Group C was treated with 5 mg 路kg ~ (-1) of normal saline group, and 0.5 mg 路kg ~ (-1) 路kg ~ (-1) of normal saline group, and the method of administration was intramuscular injection to the left hind limb. The medicine is given once a day in the morning. Each group was killed at 14d and 42d respectively. Liver was taken and embedded in paraffin wax. 1. The structure of hepatic lobule and hepatic cell fatty degeneration and vacuolar degeneration were observed by HE staining. The changes of hepatic fatty acid synthase positive cells were determined by immunohistochemical method. 3. The content of fatty acid synthase in rat liver was quantitatively detected by Western Blot method. Results: after 1.HE staining, it was observed that the hepatic sinusoids became narrow, disappeared, the hepatic cord dissociated and the structure disappeared, the liver cells were swollen, turbid, and lipid droplets appeared in the cytoplasm of the liver. Large lipid droplets deform the nucleus; hepatocytes present local, partial or diffuse steatosis; in severe cases, hepatocyte balloon degeneration is seen, the boundary is unclear, and nuclear pyknosis can be seen. The severity of toxicity increased with time and dose. 2. Immunohistochemical results showed that the cytoplasm of fatty acid synthase positive cells in rat liver was yellow staining. The results of 3.Western Blot showed that the content of fatty acid synthase decreased with the increase of time and dose. Conclusion: AP has obvious toxic effects on liver, mainly manifested as steatosis and edema of hepatocytes, and was proved by immunohistochemistry and Western blotting. The cell number and content of fatty acid synthase decreased with the increase of time and dose of AP.
【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】：2007
【分類號(hào)】：R363

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