三丁基锡的免疫毒性研究

发布时间：2018-05-07 19:06

本文选题：三丁基锡 + 小鼠　；参考：《浙江大学》2012年硕士论文

【摘要】：三丁基锡(TBT)曾经广泛用于防止海洋附着生物对船体、鱼网、钻井平台等的污损,由于其不断释放入周围水体并沉降入海泥中,对其它非靶标生物也产生了严重的危害,包括通过食物链危害人类。目前已被联合国环境保护署归入持久性有毒物质之一,国际海事组织已经规定2008年后停止使用。即便如此,由于其稳定性和高残留性,它的危害还将持续很久。因此研究其毒性作用及毒性评价方法仍然十分重要。TBT具有多系统毒性,包括免疫毒性、神经毒性及内分泌作用,其细胞水平的作用机制是诱导细胞凋亡。本研究探讨了TBT对小鼠的免疫毒性,包括检测不同浓度染毒96小时时TBT对胸腺和脾脏的影响。用TUNEL方法检测其对胸腺组织细胞凋亡的影响,用蛋白磷酸酶2A活性测定方法检测脾脏组织该酶的活性。结果表明,96小时染毒,胸腺组织在TBT剂量为60mg/kg时出现明显的细胞凋亡,而相对低剂量的TBT染毒没有明显影响胸腺组织的细胞凋亡；脾脏组织的蛋白磷酸酶2A活性在各实验组均有降低并呈剂量依赖性,在TBT剂量为60mg/kg时具有显著性差异。研究证实：TBT短时间染毒对小鼠胸腺有明显的干扰细胞凋亡的作用,对脾脏蛋白磷酸酶2A活性有极为明显的抑制作用。研究一方面进一步证实了TBT的免疫毒性,同时也证明蛋白磷酸酶2A作为免疫系统中各重要信号通路的调节蛋白可以灵敏反映TBT的影响,是一种有潜在应用前景的生物标志物。
[Abstract]:Three Ding Ji tin tins (TBT) has been widely used to prevent the fouling of ships, fishing nets and drilling platforms by marine adherent organisms. Due to its continuous release into the surrounding water and settling into the sea mud, it has also caused serious harm to other non-target organisms. Including harm to mankind through the food chain. Currently classified as one of the persistent toxic substances by the United Nations Environmental Protection Agency, the International Maritime Organization (IMO) has banned use after 2008. Even so, because of its stability and high residue, its damage will continue for a long time. Therefore, it is still very important to study its toxicity and toxicity evaluation methods. TBT has multi-system toxicity, including immune toxicity, neurotoxicity and endocrine effect. The mechanism of its cytotoxicity is to induce apoptosis. The immunotoxicity of TBT on mice was studied, including the effects of TBT on thymus and spleen at 96 hours of exposure to different concentrations. TUNEL method was used to detect the apoptosis of thymocytes and the activity of protein phosphatase 2A was used to detect the activity of this enzyme in spleen tissue. The results showed that the apoptosis of thymus tissue was obvious when the dose of TBT was 60mg/kg at 96 h, but the apoptosis of thymus tissue was not affected by the low dose of TBT. The activity of protein phosphatase 2A in spleen tissue decreased in a dose-dependent manner in all experimental groups, and there was significant difference when the dose of TBT was 60mg/kg. It was confirmed that TBT could interfere with the apoptosis of mouse thymus and inhibit the activity of protein phosphatase 2A in spleen. On the one hand, the immunotoxicity of TBT was further confirmed, but also the role of protein phosphatase 2A as a regulatory protein in various important signaling pathways in the immune system was proved to be sensitive to the effect of TBT, which is a potential biomarker.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R114

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