二维纳米材料对免疫细胞炎症反应及其病原微生物清除功能的影响及机理
批准号:
42077394
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
张雪娇
依托单位:
学科分类:
环境与健康风险
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
张雪娇
中文摘要
病原微生物在环境中无处不在,严重威胁着人类的健康。巨噬细胞作为机体免疫系统的重要组成部分,在抵抗病原微生物入侵时发挥了重要的防御作用。巨噬细胞不仅能清除病原微生物,还能对纳米材料进行识别和响应。随着二维纳米材料的大量生产和使用,学者们已经对这类材料的毒性进行了深入研究,但关于其影响机体免疫系统功能,干扰炎症反应,进而影响病原微生物易感性的间接健康风险还未见报道。因此,本项目拟选取用途广泛的石墨烯、氧化石墨烯、二硫化钼和二维黑磷等二维纳米材料,定性及定量研究二维纳米材料与细胞膜的物理相互作用和细胞内化过程对巨噬细胞炎症反应的影响和机理,建立二维纳米材料性质与其免疫学效应的构效关系,揭示二维纳米材料对巨噬细胞清除病原微生物功能的影响机制,为二维纳米材料的风险评估提供理论依据和数据支持,对制定二维纳米材料的使用安全规范,降低环境暴露和健康风险具有指导意义。
英文摘要
Pathogens are ubiquitous in nature, which pose a serious threat to human beings. Macrophage, as an important component of body’s immune system, plays a crucial role in defending against pathogen infection. Besides pathogen clearance, macrophage can also recognize and response to nanomaterials. With the extensive production and application of two-dimensional (2D) nanomaterials, researchers have been working on the investigation of their toxicity. However, there have been no reports till now with regard to the indirect health risk of 2D nanomaterials, for instance, the effects on the immune system function, the inflammatory response, and then the susceptibility to pathogen infection. Therefore, graphene, graphene oxide, 2D molybdenum disulfide, and 2D black phosphorus, which have wide prospect for application, are selected in this project as representative 2D nanomaterials. We will focus on both qualitative and quantitative investigations of the physical interactions between 2D nanomaterials and cell membrane, the internalization process, and the subsequent effects on macrophage inflammatory response. Meanwhile, the correlation between the properties of 2D nanomaterials and their immunological effect will be constructed. Importantly, the underneath mechanisms of materials’ influence on the pathogen clearance capacity of macrophage will be explored. The results will not only provide theoretical basis and data support for the risk assessment of 2D nanomaterials, but also be guidance for establishing their safety code for use and reducing the environmental exposure as well as the health risk.
巨噬细胞不仅能清除病原微生物,还能对纳米材料进行识别和响应。作为“后石墨烯时代”的明星材料,二维黑磷在诸多领域都有着广泛应用,其环境排放和人体暴露不可避免。现有研究大多关注二维黑磷的直接毒性,而关于其影响机体免疫系统功能,干扰炎症反应,进而影响病原菌易感性的间接健康风险还未见报道。因此,本项目以RAW264.7巨噬细胞为研究对象,探究了二维黑磷对巨噬细胞自噬、极化及病原菌清除功能的影响,发现了二维黑磷能够降低线粒体的功能和完整性,诱导 NAD+/NADH 水平升高,上调 SIRT-1蛋白,激活细胞自噬,造成自噬小体积累,并通过破坏溶酶体的功能和完整性,造成自噬通量堵塞;还能激活ROS/NF-κB 通路,促进巨噬细胞向M1极化,从而增强其病原菌吞噬能力;由于溶酶体功能被破坏,病原菌被保护在自噬小体中,抑制了巨噬细胞对病原菌的消化功能。因此,二维黑磷降低了巨噬细胞对病原菌的抵抗能力。本研究为二维黑磷的健康风险评估提供了理论依据。
二维纳米材料的理化性质与其环境行为和微生物毒性的相关性研究
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批准号:41877389
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项目类别:面上项目
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资助金额:61.0万元
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批准年份:2018
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负责人:张雪娇
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依托单位:
mPEG-PLA纳米胶束与DDT的吸附作用及其复合毒性效应
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批准号:41603120
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项目类别:青年科学基金项目
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资助金额:20.0万元
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批准年份:2016
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负责人:张雪娇
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依托单位:
国内基金
海外基金