多氯联苯醌介导的HepG2细胞内氧化应激及硫辛酸拮抗自由基的研究

发布时间：2018-10-11 19:57

【摘要】：多氯联苯(PCBs)是人工合成的有机化合物,自20世纪20年代末开始生产和陆续大量使用以来,已逐渐地残留在人们周围的大气、水体和土壤环境中,其污染范围非常广泛。PCBs作为典型的持久性有机污染物具备难降解性、生物毒性、生物蓄积性、远距离迁移性的特征。它具有稳定的物理化学性质,属半挥发或不挥发物质,及较强的腐蚀性。尽管PCBs性质稳定,但是在细胞色素P450酶的催化作用下仍然可以代谢为羟基化多氯联苯,再进一步氧化为高活性的多氯联苯醌。大量的研究表明PCBs能引起细胞的氧化应激,但对PCBs的代谢产物——多氯联苯醌引起氧化应激的研究还处于空白。因此,直接研究多氯联苯醌对细胞的氧化应激作用非常必要。生物体内的抗氧化系统在清除自由基和抑制氧化应激中发挥着重要作用。抗氧化剂作为自由基清除剂,可以有效补充体内抗氧化剂的不足,在保护机体氧化还原平衡等发面发挥着显著的作用。研究表明,外源性引起的细胞氧化应激和凋亡等损伤都能在抗氧化剂的作用下得到一定的缓解。硫辛酸作为一种既脂溶,又水溶的抗氧化剂,对机体有明显的保护作用。本文主要的工作如下：以HepG2细胞系为载体,通过研究四种不同氯原子位置和数目的多氯联苯醌的暴露对细胞存活率、活性氧水平、脂质过氧化产物、超氧化物歧化酶,过氧化氢酶、谷胱甘肽和谷胱甘肽转移酶等指标的改变,探讨PCBQ介导的氧化应激相关的细胞毒性作用；同时研究了硫辛酸拮抗自由基的能力。以上研究表明,多氯联苯醌能够引起细胞的氧化应激。PCBQ降低了细胞的存活率,增强了细胞内的活性氧、脂质过氧化水平,增强了超氧化物歧化酶的活力,但过氧化氢酶活力、谷胱甘肽及谷胱甘肽转移酶活力有所降低。在抗氧化剂硫辛酸的存在下,PCBQ带来的细胞内氧化应激得到了一定程度的缓解。同时我们发现,在所选择的四个PCBQ化合物之间存在一定的结构活性关系,其中以3C1-PCBQ的引起细胞内氧化应激和细胞毒性效应最强。
[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.
【学位授予单位】：西南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R114

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