本文關(guān)鍵詞： 鄰苯二甲酸二丁酯 核磁共振 代謝組學 毒性　出處：《廣東藥科大學》2017年碩士論文　論文類型：學位論文

【摘要】：鄰苯二甲酸二丁酯(DBP)作為增塑劑已在各個領(lǐng)域廣泛使用,但其潛在的毒性同樣受到大眾的關(guān)注。本課題以分子生物學與生物化學的理論為基礎(chǔ),采用核磁共振代謝組學方法,與病理組織學檢查與血漿生化分析等傳統(tǒng)毒理學方法。研究經(jīng)DBP染毒情況下大鼠生物體液中的內(nèi)源性代謝物的動態(tài)變化情況,說明機體內(nèi)產(chǎn)生的代謝應(yīng)答與內(nèi)在組織損傷之間的關(guān)系,進而闡述DBP的毒性作用機理。代謝組學數(shù)據(jù)的模式識別分析結(jié)果顯示,DBP染毒后大鼠各生物體液中的內(nèi)源性代謝產(chǎn)物的變化情況相比對照組具有顯著性的差異。血漿生化指標分析結(jié)果表明肝腎功能受損,病理組織學檢查也說明睪丸、肝腎組織有損傷。并且血漿生化分析及病理組織學檢查得出的結(jié)果與體內(nèi)代謝物的差異情況與表現(xiàn)出統(tǒng)一性。DBP染毒劑量組與對照組比較,產(chǎn)生的內(nèi)源性代謝物的變化情況主要包括:(1)血漿中乳酸、丙酮酸水平升高;脂質(zhì)蛋白、β-羥丁酸鹽、糖蛋白、檸檬酸、葡萄糖、磷酸肌酸、不飽和脂肪酸、酪氨酸和苯丙氨酸水平下降。(2)尿液中亮氨酸、異亮氨酸、纈氨酸、β-羥基丁酸、丙氨酸、賴氨酸、乙酸鹽、馬尿酸和色氨酸的水平升高;乳酸、糖蛋白、蛋氨酸、丙酮、α-酮戊二酸、谷氨酰胺、檸檬酸、丙二酸鹽、膽堿、氧化三甲胺(TMAO)、�；撬�、肌酸、肌酸酐、β-葡萄糖、順烏頭酸、異檸檬酸、蘋果酸和甲酸鹽水平下降。(3)糞樣中的亮氨酸、異亮氨酸、色氨酸、纈氨酸、丙氨酸、乙酸鹽、賴氨酸和腺嘌呤的水平升高;乳酸、糖蛋白、蛋氨酸、α-酮戊二酸、谷氨酰胺、丙二酸鹽、膽堿、氧化三甲胺、�；撬�、肌酸、β-葡萄糖、蘋果酸和甲酸鹽水平下降。并且,大鼠機體內(nèi)這些代謝物的差異變化情況存在劑量和時間的毒效關(guān)系。參考衛(wèi)生毒理學、病理組織學和生物化學等理論進行分析,得出DBP導(dǎo)致的代謝物差異變化可相對的造成機體某些代謝途徑發(fā)生紊亂,其中包括三羧酸循環(huán)(檸檬酸循環(huán))、糖類代謝,蛋白質(zhì)代謝和脂質(zhì)代謝等,且還提示體內(nèi)腸道菌群存在失衡的情況。并且這些生化代謝途徑的紊亂與DBP的毒性作用呈一定程度的相關(guān)性。本研究能夠全面監(jiān)測DBP毒性作用的產(chǎn)生、發(fā)展及蓄積的整個過程,從整體水平上系統(tǒng)闡述DBP引起的毒性作用機制,為環(huán)境化學物質(zhì)的毒理學研究提供新方法。
[Abstract]:Dibutyl phthalate (DBP) as a plasticizer has been widely used in various fields, but its potential toxicity is also concerned by the public. This topic is based on the theory of molecular biology and biochemistry. The dynamic changes of endogenous metabolites in the biological fluid of rats exposed to DBP were studied by traditional toxicological methods such as nuclear magnetic resonance metabonomics, histopathology and plasma biochemical analysis. The relationship between metabolic response and internal tissue damage was explained, and the toxic mechanism of DBP was explained. The results of pattern recognition analysis of metabolomics data showed that. The changes of endogenous metabolites in the fluid of rats exposed to DBP were significantly different from those in the control group. The results of plasma biochemical index analysis showed that the liver and kidney function was damaged. Histopathological examination also indicates that the testicles. The results of biochemical analysis and histopathology of plasma were different from those of metabolites in the body and showed the unity between the group treated with DBP and the control group. The changes of endogenous metabolites mainly included the increase of lactate and pyruvate levels in plasma. The levels of lipid protein, 尾 -hydroxybutyrate, glycoprotein, citric acid, glucose, creatine phosphate, unsaturated fatty acid, tyrosine and phenylalanine decreased in urine. The levels of 尾 -hydroxybutyric acid, alanine, lysine, acetate, hippuric acid and tryptophan increased. Lactic acid, glycoprotein, methionine, acetone, 偽 -ketoglutaric acid, glutamine, citric acid, malonate, choline, trimethylamine oxide TMAOO, taurine, creatine, creatinine, 尾 -glucose. The levels of leucine, isoleucine, tryptophan, valine, alanine, acetate, lysine and adenine in fecal samples decreased. Levels of lactic acid, glycoprotein, methionine, 偽 -ketoglutaric acid, glutamine, malonate, choline, trimethylamine oxide, taurine, creatine, 尾 -glucose, malic acid and formate decreased. The difference of these metabolites in the body of rats was related to dose and time. The results were analyzed with reference to the theories of health toxicology, histopathology and biochemistry. It is concluded that the difference of metabolites caused by DBP can cause disorder of some metabolic pathways, including tricarboxylic acid cycle (citric acid cycle), carbohydrate metabolism, protein metabolism and lipid metabolism. It is also suggested that there is imbalance in intestinal flora in vivo, and the disturbance of these biochemical metabolic pathways is related to the toxicity of DBP to some extent. This study can comprehensively monitor the production of toxic effects of DBP. In order to provide a new method for toxicological study of environmental chemicals, the mechanism of toxicity induced by DBP is systematically expounded in the whole process of development and accumulation.
【學位授予單位】：廣東藥科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R114

【參考文獻】

相關(guān)期刊論文 前10條

1 何盼;李震宇;范圣此;張福生;秦雪梅;杜國軍;;基于代謝組學技術(shù)和ITS2序列的恒山黃芪與川黃芪差異性研究[J];藥學學報;2013年10期

2 葉文華;龔夢鵑;鄒忠杰;;巴戟天抗炎作用的代謝組學研究[J];中藥與臨床;2013年03期

3 鄒忠杰;龔夢鵑;王淑美;梁生旺;;雙黃連口服液抗炎作用的代謝組學研究[J];中成藥;2013年01期

4 李英帥;王琦;袁卓s，

本文編號：1446992