细胞骨架相关的微囊藻毒素毒性机理研究

发布时间：2018-01-15 21:01

本文关键词：细胞骨架相关的微囊藻毒素毒性机理研究　出处：《宁波大学》2012年硕士论文　论文类型：学位论文

【摘要】：近年来，经济快速发展的同时也带来了日趋严重的环境污染，水体富营养化问题尤为突出，我国的许多湖泊、河流频频暴发蓝藻水华。蓝藻水华暴发时，藻类释放大量毒素进入水体，铜绿微囊藻释放的微囊藻毒素（Microcystin，，MC）是其中含量最高、毒性最大、危害最广的一类毒素。MC主要靶器官是肝脏，是一种确认的肝毒素，可引起肝脏急性出血、肝坏死和原发性肝癌。MC-LR诱导的肝细胞毒性及强促癌性的分子机制已有了广泛的研究，并取得了一定成果。但是MC毒性机制尚未完全阐明，尤其是细胞骨架系统在MC毒性效应机制中的作用并不明确。因此本研究以细胞骨架为研究对象，选择人来源的正常肝细胞系HL7702进行MC-LR的毒性机理研究。用不同浓度的MC-LR染毒处理HL7702细胞24h后，首先检测MC-LR对HL7702细胞的整体毒性效应，包括MC-LR对细胞形态、细胞增殖、细胞周期、细胞凋亡和细胞骨架的影响，并进一步研究MC-LR处理后骨架蛋白编码基因转录水平以及蛋白表达水平和共价修饰的变化。研究发现MC-LR可明显抑制细胞增殖并诱导细胞凋亡，同时引起中间纤维和微丝结构发生明显改变。骨架蛋白K8/18、Vimentin、VASP的磷酸化水平显著升高，但相关编码基因的转录和翻译水平并无显著改变。这些结果提示，细胞骨架蛋白磷酸化水平增加可能与细胞骨架结构变化及细胞凋亡存在关联。同时Keratin8/18、Vimentin、VASP等蛋白参与多种信号途径，这也为我们进一步深入研究MC-LR破坏细胞骨架的机理，以及通过哪些骨架相关蛋白及信号途径引起更广泛的毒性效应等问题提供线索。
[Abstract]:In recent years, rapid development of economy has brought increasingly serious environmental pollution, water eutrophication problem is particularly prominent, many of China's rivers and lakes, frequent outbreaks of algal blooms. Cyanobacteria bloom algae, releasing large amounts of toxins into the water, microcystin release of Microcystis aeruginosa (Microcystin, MC) is one of content is the highest, the most toxic, a toxoid.MC main target organ damage is the most widely recognized of the liver, is a liver toxin, can cause acute hemorrhage of liver, the molecular mechanism of liver cell toxicity and liver necrosis and hepatocellular carcinoma.MC-LR induced cancer promoting the extensive research, and achieved certain results. But MC toxicity mechanism has not been fully elucidated, especially the role of the cytoskeleton in the mechanism of MC toxicity is not clear. This study takes the cytoskeleton as the research object, select the source of normal people Liver cell line HL7702 were studied. The toxicity mechanism of MC-LR with different concentration of MC-LR treated HL7702 cells 24h after the first detection of MC-LR on HL7702 cells overall toxic effects, including MC-LR on cell morphology, cell proliferation, cell cycle, apoptosis and cytoskeleton influence, and further study after treatment with MC-LR skeleton protein encoding the level of gene transcription and protein expression level changes and covalent modification. Research found that MC-LR can inhibit cell proliferation and induce cell apoptosis, and the cause of intermediate filaments and microfilament structure changed obviously. The skeleton protein K8/18, Vimentin, VASP phosphorylation levels were significantly increased, but the gene encoding the transcription and translation levels were not significantly changed. These results suggest that the increase in cytoskeletal protein phosphorylation may be associated with cytoskeletal structure changes and apoptosis and Keratin8. /18, Vimentin, VASP and other proteins are involved in multiple signaling pathways. This is also helpful for us to further study the mechanism of MC-LR destroying the cytoskeleton and provide clues for the wider toxic effects of skeleton related proteins and signaling pathways.

【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R123.1

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