本文選題：硫丹　切入點：HUVEC-C細胞　出處：《大連海事大學》2017年碩士論文

【摘要】：硫丹是一種應用廣泛的有機氯農藥,在2011年被斯德哥爾摩公約列為持久性有機污染物,在環(huán)境介質中廣泛存在,具有高毒性、持久性、生物富集性、可長距離傳輸的特點,因此,其對人類健康的遠期危害不能被忽視。前期研究發(fā)現(xiàn)硫丹具有血管內皮細胞毒性,能夠引起血管內皮細胞周期阻滯、凋亡和炎癥反應,導致血管內皮細胞功能失調,考慮可能與人類疾病關系密切。為了揭示硫丹暴露引起血管內皮細胞功能失調的分子機制及與人類疾病的關系,本課題探討了硫丹對血管內皮細胞基因表達譜的影響并進行了人類疾病預測分析。本研究采用DNA microarray分析了硫丹暴露(20,40,60μM)對HUVEC-C細胞的基因表達譜的影響,利用GO分析和KEGG Pathway探討了硫丹暴露引起的HUVEC-C細胞表型變化與基因表達變化間的關聯(lián),進一步聯(lián)合NextBio和Metacore數據庫預測了與硫丹暴露最相關的人類疾病、心血管疾病和癌癥;篩選了促進前列腺癌發(fā)展的關鍵基因,最后驗證了硫丹促進前列腺癌發(fā)展的作用及其關鍵基因的功能。結果表明,硫丹能夠引起差異表達的基因數量增加,具有劑量依賴性關系。硫丹引起多種生物學過程和信號通路發(fā)生變化與硫丹引起血管內皮細胞損傷的表型變化一致。低劑量硫丹(20μM)暴露引起下調的基因主要涉及細胞骨架調節(jié),較高劑量(40μM和60μM)硫丹暴露引起下調的基因涉及細胞周期和凋亡而上調的基因涉及炎癥反應和癌的轉錄失調信號通路。硫丹暴露與人類的消化系統(tǒng)疾病、代謝疾病、心血管疾病和癌癥相關。其中最相關的癌癥是肝癌、前列腺癌和白血病。硫丹促進前列腺癌發(fā)展的關鍵基因是PTP4A3,可能通過提高PTP4A3的mRNA表達水平而促進前列腺癌的遷移能力。這項研究將為揭示硫丹暴露引起人類疾病的分子機制提供新的依據。
[Abstract]:Endosulfan, a widely used organochlorine pesticide, was listed as a persistent organic pollutant by the Stockholm Convention in 2011. It is widely present in environmental media and has the characteristics of high toxicity, persistence, bioconcentration and long distance transport. Therefore, its long-term harm to human health can not be ignored. Previous studies have found that endosulfan has vascular endothelial cell toxicity, can cause vascular endothelial cell cycle arrest, apoptosis and inflammation, leading to vascular endothelial cell dysfunction, In order to reveal the molecular mechanism of vascular endothelial cell dysfunction caused by endosulfan exposure and its relationship with human disease, In this study, the effect of endosulfan on gene expression profile of vascular endothelial cells (VECs) and the prediction of human disease were studied. DNA microarray was used to analyze the effect of endosulfan exposure on the gene expression profile of HUVEC-C cells. Go analysis and KEGG Pathway were used to explore the relationship between phenotypic changes and gene expression changes in HUVEC-C cells induced by endosulfan exposure. Furthermore, combined with NextBio and Metacore databases, the most relevant human diseases, cardiovascular diseases and cancer were predicted. The key genes for the development of prostate cancer were screened, and the role of endosulfan in promoting the development of prostate cancer and the function of the key genes were verified. The results showed that endosulfan could cause an increase in the number of differentially expressed genes, The changes in many biological processes and signal pathways induced by endosulfan are consistent with the phenotypic changes in vascular endothelial cell injury induced by endosulfan. The down-regulated genes induced by exposure to low-dose endosulfan 20 渭 M mainly involve cytoskeletal regulation. Exposure to endosulfan at a higher dose of 40 渭 M and 60 渭 M involves down-regulated genes related to cell cycle and apoptosis, while up-regulated genes involve inflammatory responses and transcriptional dysfunctional signaling pathways of cancer. Endosulfan exposure is associated with diseases of the human digestive system, metabolic diseases, Cardiovascular disease is associated with cancer. The most relevant cancer is liver cancer. Prostate cancer and leukemia. The key gene that endosulfan promotes the development of prostate cancer is PTP4A3, which may promote the migration of prostate cancer by increasing the level of mRNA expression of PTP4A3. This study will be used to reveal that endosulfan exposure causes human disease. To provide a new basis for the molecular mechanism.
【學位授予單位】：大連海事大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R114

【相似文獻】

相關期刊論文 前10條

1 袁文博;相秉仁;趙陸華;于麗燕;;番茄表層硫丹殘留的近紅外快速檢測方法[J];中國藥科大學學報;2012年02期

2 謝建軍;紀春艷;陳捷;王嵐;林峰;焦紅;;氣相色譜法快速測定鰻魚中殘留的硫丹代謝物-硫丹硫酸酯[J];中國衛(wèi)生檢驗雜志;2008年10期

3 覃玲;羅光毅;蔡超海;;固相萃取-氣相色譜法測定魚肉中硫丹殘留量[J];中國衛(wèi)生檢驗雜志;2010年12期

4 陳俊青;黃曉軍;崔巍;;急性重度硫丹中毒1例[J];全科醫(yī)學臨床與教育;2006年05期

5 Gupta PK;朱國棟;;硫丹的藥理毒理和代謝[J];國外醫(yī)學(衛(wèi)生學分冊);1980年04期

6 謝立t，

本文編號：1657056