项目名称： microRNA在微囊藻毒素抑制哺乳动物造血功能中的作用机制

项目编号： No.31500442

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 周文珊

作者单位： 郑州轻工业学院

项目金额： 20万元

中文摘要： 水体富营养化引起水体大规模暴发蓝藻水华，蓝藻细胞破裂后向水体中释放多种有毒的藻毒素，而微囊藻毒素（Microcystin, MC）是其中出现频率最高、产生量最大和造成危害最严重的一类。已有的研究证实MC具有多器官毒性效应，能造成机体贫血，骨髓细胞增殖活力下降并引起遗传毒性，但是对于其抑制动物造血功能的分子机理目前尚不明确。本项目通过建立小鼠贫血动物模型和骨髓基质细胞毒理模型，采用传统毒理学方法观察MC染毒后致其发生贫血效应和相关的生理学、病理学变化。并首次结合现代毒理学方法，采用基因组学、生物信息学的分析方法揭示小鼠microRNA表达变化规律、利用蛋白质组学技术揭示MC对小鼠骨髓基质细胞蛋白质表达的变化规律，最终阐明microRNA在微囊藻毒素抑制哺乳动物造血机能中的作用及其分子机制，从而为流行病学研究提供更丰富的试验证据，为风险评估和安全管理提供更直接和可参考的实验证据。

中文关键词： 微囊藻毒素；贫血；造血机能；小RNA；细胞凋亡

英文摘要： Water eutrophication caused cyanobaterial blooms, then a variety of cyanotoxins were released to water by cyanobacteria cells which have caused a great threat to the ecological environment and human health. Among cyanotoxins, the microcystins (MCs) are the most common and toxic group. Previous studies have shown MCs are hepatotoxicity, renal toxicity, immune toxicity, reproductive toxicity, developmental toxicity and potential cancer-promoting activity. There were some studies about anemia caused by MC-LR which are concentrated in the hematological indices, the proliferation of bone marrow cells, genetic toxicity and so on, but the mechanism research about inhibition of hematopoietic function is still unclear. In this study, we observe the anemia and related physiological、pathological changes, using traditional toxicological methods by mice anemic model and cell toxicological model when the mice ( bone marrow stromal cell ) exposed to MC-LR. Firstly, we reveal the variation of mice microRNA expression level by genomics technique and bioinformatics analysis. Then we evaluate the variation of bone marrow stromal cell protein expression level by proteomics technique. Eventually, we clarify the molecular mechanisms of microRNA in inhibition of hematopoietic function when mammalian exposed to microcystin-LR, so as to provide more trial evidence for epidemiological studies, risk assessment and safety management.

英文关键词： microcystin;anemia;hematopoietic function;microRNA;cell apoptosis