本文關(guān)鍵詞：細(xì)胞骨架相關(guān)的微囊藻毒素毒性機(jī)理研究　出處：《寧波大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 微囊藻毒素 肝細(xì)胞 細(xì)胞周期 細(xì)胞凋亡 細(xì)胞骨架 磷酸化

【摘要】：近年來，經(jīng)濟(jì)快速發(fā)展的同時(shí)也帶來了日趨嚴(yán)重的環(huán)境污染，水體富營養(yǎng)化問題尤為突出，我國的許多湖泊、河流頻頻暴發(fā)藍(lán)藻水華。藍(lán)藻水華暴發(fā)時(shí)，藻類釋放大量毒素進(jìn)入水體，銅綠微囊藻釋放的微囊藻毒素（Microcystin，，MC）是其中含量最高、毒性最大、危害最廣的一類毒素。MC主要靶器官是肝臟，是一種確認(rèn)的肝毒素，可引起肝臟急性出血、肝壞死和原發(fā)性肝癌。MC-LR誘導(dǎo)的肝細(xì)胞毒性及強(qiáng)促癌性的分子機(jī)制已有了廣泛的研究，并取得了一定成果。但是MC毒性機(jī)制尚未完全闡明，尤其是細(xì)胞骨架系統(tǒng)在MC毒性效應(yīng)機(jī)制中的作用并不明確。因此本研究以細(xì)胞骨架為研究對(duì)象，選擇人來源的正常肝細(xì)胞系HL7702進(jìn)行MC-LR的毒性機(jī)理研究。用不同濃度的MC-LR染毒處理HL7702細(xì)胞24h后，首先檢測MC-LR對(duì)HL7702細(xì)胞的整體毒性效應(yīng)，包括MC-LR對(duì)細(xì)胞形態(tài)、細(xì)胞增殖、細(xì)胞周期、細(xì)胞凋亡和細(xì)胞骨架的影響，并進(jìn)一步研究MC-LR處理后骨架蛋白編碼基因轉(zhuǎn)錄水平以及蛋白表達(dá)水平和共價(jià)修飾的變化。研究發(fā)現(xiàn)MC-LR可明顯抑制細(xì)胞增殖并誘導(dǎo)細(xì)胞凋亡，同時(shí)引起中間纖維和微絲結(jié)構(gòu)發(fā)生明顯改變。骨架蛋白K8/18、Vimentin、VASP的磷酸化水平顯著升高，但相關(guān)編碼基因的轉(zhuǎn)錄和翻譯水平并無顯著改變。這些結(jié)果提示，細(xì)胞骨架蛋白磷酸化水平增加可能與細(xì)胞骨架結(jié)構(gòu)變化及細(xì)胞凋亡存在關(guān)聯(lián)。同時(shí)Keratin8/18、Vimentin、VASP等蛋白參與多種信號(hào)途徑，這也為我們進(jìn)一步深入研究MC-LR破壞細(xì)胞骨架的機(jī)理，以及通過哪些骨架相關(guān)蛋白及信號(hào)途徑引起更廣泛的毒性效應(yīng)等問題提供線索。
[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.

【學(xué)位授予單位】：寧波大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R123.1

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本文編號(hào)：1430021