多氯聯(lián)苯醌介導的HepG2細胞內氧化應激及硫辛酸拮抗自由基的研究
發(fā)布時間：2018-10-11 19:57
【摘要】：多氯聯(lián)苯(PCBs)是人工合成的有機化合物,自20世紀20年代末開始生產(chǎn)和陸續(xù)大量使用以來,已逐漸地殘留在人們周圍的大氣、水體和土壤環(huán)境中,其污染范圍非常廣泛。PCBs作為典型的持久性有機污染物具備難降解性、生物毒性、生物蓄積性、遠距離遷移性的特征。它具有穩(wěn)定的物理化學性質,屬半揮發(fā)或不揮發(fā)物質,及較強的腐蝕性。盡管PCBs性質穩(wěn)定,但是在細胞色素P450酶的催化作用下仍然可以代謝為羥基化多氯聯(lián)苯,再進一步氧化為高活性的多氯聯(lián)苯醌。大量的研究表明PCBs能引起細胞的氧化應激,但對PCBs的代謝產(chǎn)物——多氯聯(lián)苯醌引起氧化應激的研究還處于空白。因此,直接研究多氯聯(lián)苯醌對細胞的氧化應激作用非常必要。 生物體內的抗氧化系統(tǒng)在清除自由基和抑制氧化應激中發(fā)揮著重要作用�？寡趸瘎┳鳛樽杂苫宄齽�,可以有效補充體內抗氧化劑的不足,在保護機體氧化還原平衡等發(fā)面發(fā)揮著顯著的作用。研究表明,外源性引起的細胞氧化應激和凋亡等損傷都能在抗氧化劑的作用下得到一定的緩解。硫辛酸作為一種既脂溶,又水溶的抗氧化劑,對機體有明顯的保護作用。 本文主要的工作如下：以HepG2細胞系為載體,通過研究四種不同氯原子位置和數(shù)目的多氯聯(lián)苯醌的暴露對細胞存活率、活性氧水平、脂質過氧化產(chǎn)物、超氧化物歧化酶,過氧化氫酶、谷胱甘肽和谷胱甘肽轉移酶等指標的改變,探討PCBQ介導的氧化應激相關的細胞毒性作用；同時研究了硫辛酸拮抗自由基的能力。 以上研究表明,多氯聯(lián)苯醌能夠引起細胞的氧化應激。PCBQ降低了細胞的存活率,增強了細胞內的活性氧、脂質過氧化水平,增強了超氧化物歧化酶的活力,但過氧化氫酶活力、谷胱甘肽及谷胱甘肽轉移酶活力有所降低。在抗氧化劑硫辛酸的存在下,PCBQ帶來的細胞內氧化應激得到了一定程度的緩解。同時我們發(fā)現(xiàn),在所選擇的四個PCBQ化合物之間存在一定的結構活性關系,其中以3C1-PCBQ的引起細胞內氧化應激和細胞毒性效應最強。
[Abstract]:Polychlorinated biphenyls (PCBs) are synthetic organic compounds. Since they were produced and used in large quantities in the late 1920s, PCBs have gradually remained in the atmosphere, water and soil environment around people. As a typical persistent organic pollutant, PCBs has the characteristics of non-degradability, biotoxicity, bioaccumulation and long-range migration. It has stable physical and chemical properties, is semi-volatile or non-volatile, and strong corrosion. Although the properties of PCBs are stable, it can be metabolized as hydroxylated PCBs under the catalysis of cytochrome P450 enzyme and further oxidized to highly active PCBs quinone. A large number of studies have shown that PCBs can induce oxidative stress in cells, but the study of oxidative stress induced by PCB-quinone, the metabolite of PCBs, is still in the blank. Therefore, it is necessary to study the oxidative stress of PCB quinone directly. The antioxidant system plays an important role in scavenging free radicals and inhibiting oxidative stress. As a free radical scavenger, antioxidants can effectively supplement the deficiency of antioxidants in vivo and play a significant role in protecting the redox balance. The results showed that oxidative stress and apoptosis could be alleviated by antioxidants. Lipoic acid, as a kind of lipid-soluble and water-soluble antioxidant, has obvious protective effect on the body. The main work of this paper is as follows: the cell viability, reactive oxygen species, lipid peroxidation products, superoxide dismutase, superoxide dismutase (SOD) were studied by exposure to four different chlorinated quinone sites and number of PCBs in HepG2 cell line. The changes of catalase, glutathione and glutathione transferase were used to study the cytotoxicity related to oxidative stress mediated by PCBQ and the ability of lipoic acid to antagonize free radical. The results showed that PCB could induce oxidative stress. PCBQ decreased cell survival, increased reactive oxygen species, lipid peroxidation, and superoxide dismutase activity, but catalase activity. The activities of glutathione and glutathione transferase were decreased. In the presence of the antioxidant lipoic acid, intracellular oxidative stress induced by PCBQ was alleviated to a certain extent. At the same time, we found that there was a certain relationship between the four selected PCBQ compounds, among which the 3C1-PCBQ had the strongest effect on intracellular oxidative stress and cytotoxicity.
【學位授予單位】：西南大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R114
本文編號：2265054
[Abstract]:Polychlorinated biphenyls (PCBs) are synthetic organic compounds. Since they were produced and used in large quantities in the late 1920s, PCBs have gradually remained in the atmosphere, water and soil environment around people. As a typical persistent organic pollutant, PCBs has the characteristics of non-degradability, biotoxicity, bioaccumulation and long-range migration. It has stable physical and chemical properties, is semi-volatile or non-volatile, and strong corrosion. Although the properties of PCBs are stable, it can be metabolized as hydroxylated PCBs under the catalysis of cytochrome P450 enzyme and further oxidized to highly active PCBs quinone. A large number of studies have shown that PCBs can induce oxidative stress in cells, but the study of oxidative stress induced by PCB-quinone, the metabolite of PCBs, is still in the blank. Therefore, it is necessary to study the oxidative stress of PCB quinone directly. The antioxidant system plays an important role in scavenging free radicals and inhibiting oxidative stress. As a free radical scavenger, antioxidants can effectively supplement the deficiency of antioxidants in vivo and play a significant role in protecting the redox balance. The results showed that oxidative stress and apoptosis could be alleviated by antioxidants. Lipoic acid, as a kind of lipid-soluble and water-soluble antioxidant, has obvious protective effect on the body. The main work of this paper is as follows: the cell viability, reactive oxygen species, lipid peroxidation products, superoxide dismutase, superoxide dismutase (SOD) were studied by exposure to four different chlorinated quinone sites and number of PCBs in HepG2 cell line. The changes of catalase, glutathione and glutathione transferase were used to study the cytotoxicity related to oxidative stress mediated by PCBQ and the ability of lipoic acid to antagonize free radical. The results showed that PCB could induce oxidative stress. PCBQ decreased cell survival, increased reactive oxygen species, lipid peroxidation, and superoxide dismutase activity, but catalase activity. The activities of glutathione and glutathione transferase were decreased. In the presence of the antioxidant lipoic acid, intracellular oxidative stress induced by PCBQ was alleviated to a certain extent. At the same time, we found that there was a certain relationship between the four selected PCBQ compounds, among which the 3C1-PCBQ had the strongest effect on intracellular oxidative stress and cytotoxicity.
【學位授予單位】：西南大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R114
【參考文獻】
相關期刊論文 前10條
1 李建喜;楊志強;王學智;;活性氧自由基在動物機體內的生物學作用[J];動物醫(yī)學進展;2006年10期
2 王賢;孫友敏;;多氯聯(lián)苯的污染及降解處理技術[J];化工技術與開發(fā);2010年04期
3 劉洋;冀秀玲;馬靜;徐剛;吳明紅;;上海市典型家庭室內空氣中PCBs與PBDEs初步研究[J];環(huán)境科學研究;2011年05期
4 吳水平;印紅玲;劉碧蓮;王新紅;洪麗玉;;廢棄電容器封存點及舊工業(yè)場地多氯聯(lián)苯的污染特征[J];環(huán)境科學;2011年11期
5 胡英;祁士華;張俊鵬;張蓓蓓;宋琦;;重慶地下河中多氯聯(lián)苯的分布特征及健康風險評價[J];環(huán)境科學學報;2011年08期
6 儲少崗，，徐曉白，童逸平;多氯聯(lián)苯在典型污染地區(qū)環(huán)境中的分布及其環(huán)境行為[J];環(huán)境科學學報;1995年04期
7 劉貝貝;陳劍峰;張勇;;多氯聯(lián)苯的肝毒性研究進展[J];環(huán)境與健康雜志;2009年01期
8 宋楊;吳南翔;韓見龍;沈海濤;譚玉鳳;丁剛強;項菊香;陶核;金順亮;;某電子垃圾拆解地鯽魚和雞蛋中二VA英和多氯聯(lián)苯的污染狀況研究[J];環(huán)境與健康雜志;2011年04期
9 管玉峰;涂秀云;吳宏海;;珠江入�？谒w中多氯聯(lián)苯及其歸趨分析[J];華南師范大學學報(自然科學版);2011年03期
10 葛穎華;鐘曉明;;維生素C和維生素E抗氧化機制及其應用的研究進展[J];吉林醫(yī)學;2007年05期
本文編號：2265054
本文鏈接：http://sikaile.net/yixuelunwen/yufangyixuelunwen/2265054.html
最近更新
教材專著
