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三丁基錫的免疫毒性研究

發(fā)布時(shí)間:2018-05-07 19:06

  本文選題:三丁基錫 + 小鼠; 參考:《浙江大學(xué)》2012年碩士論文


【摘要】:三丁基錫(TBT)曾經(jīng)廣泛用于防止海洋附著生物對(duì)船體、魚網(wǎng)、鉆井平臺(tái)等的污損,由于其不斷釋放入周圍水體并沉降入海泥中,對(duì)其它非靶標(biāo)生物也產(chǎn)生了嚴(yán)重的危害,包括通過食物鏈危害人類。目前已被聯(lián)合國環(huán)境保護(hù)署歸入持久性有毒物質(zhì)之一,國際海事組織已經(jīng)規(guī)定2008年后停止使用。即便如此,由于其穩(wěn)定性和高殘留性,它的危害還將持續(xù)很久。因此研究其毒性作用及毒性評(píng)價(jià)方法仍然十分重要。TBT具有多系統(tǒng)毒性,包括免疫毒性、神經(jīng)毒性及內(nèi)分泌作用,其細(xì)胞水平的作用機(jī)制是誘導(dǎo)細(xì)胞凋亡。 本研究探討了TBT對(duì)小鼠的免疫毒性,包括檢測(cè)不同濃度染毒96小時(shí)時(shí)TBT對(duì)胸腺和脾臟的影響。用TUNEL方法檢測(cè)其對(duì)胸腺組織細(xì)胞凋亡的影響,用蛋白磷酸酶2A活性測(cè)定方法檢測(cè)脾臟組織該酶的活性。結(jié)果表明,96小時(shí)染毒,胸腺組織在TBT劑量為60mg/kg時(shí)出現(xiàn)明顯的細(xì)胞凋亡,而相對(duì)低劑量的TBT染毒沒有明顯影響胸腺組織的細(xì)胞凋亡;脾臟組織的蛋白磷酸酶2A活性在各實(shí)驗(yàn)組均有降低并呈劑量依賴性,在TBT劑量為60mg/kg時(shí)具有顯著性差異。 研究證實(shí):TBT短時(shí)間染毒對(duì)小鼠胸腺有明顯的干擾細(xì)胞凋亡的作用,對(duì)脾臟蛋白磷酸酶2A活性有極為明顯的抑制作用。研究一方面進(jìn)一步證實(shí)了TBT的免疫毒性,同時(shí)也證明蛋白磷酸酶2A作為免疫系統(tǒng)中各重要信號(hào)通路的調(diào)節(jié)蛋白可以靈敏反映TBT的影響,是一種有潛在應(yīng)用前景的生物標(biāo)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.
【學(xué)位授予單位】:浙江大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R114

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