Investigating Health Effects From Exposure to Organic Carbon and Nickel Aerosol

这项工作建立在申请者K99阶段的先前培训的基础上，该阶段试图确定特定的 气溶胶中的化学成分很可能是观察到的对人类健康影响的原因。这部作品 通过探讨心血管健康的机制，满足提出的具体目标的需要 在敏感动物模型中观察老化或新鲜有机碳气溶胶暴露期间的影响 在动物模型上研究燃烧产生的富镍颗粒在心肺损伤中的作用。 这些目标符合美国国立卫生研究院更广泛的使命，通过确定与 环境污染物。 这项研究涉及一系列活体吸入暴露研究，使用的是小鼠心血管模型。 疾病。在这个项目的过程中，6组ApoE基因敲除小鼠将暴露于各种不同的 燃烧排放的气雾剂。稀释后的柴油废气将被用来模拟与环境有关的 暴露在繁忙的道路附近。该项目还包括引入一种定制的光化学产品。 老化室对气溶胶进行化学修饰，以模拟环境中的气溶胶过程。这提高了 吸入性暴露模式，通过改善暴露的环境相关性，因为 接触是新排放和年龄更大的排放的复合体。在曝光之前，每个人 老鼠将通过外科手术植入无线电遥测设备，以实时测量老鼠的活动， 体温和双导联心电图。每次暴露实验预计将进行5次 每周一次，每天6小时，持续20天。在暴露完成时，一些生物标志物 将测量端点。将收集Brionchial灌洗液并离心，上清液将 分析肺损伤的生化指标(总蛋白和乳酸脱氢酶)和炎性细胞因子。

This work builds upon previous training during the applicant's K99 phase that seeks to identify the specific chemical components of aerosol most likely responsible for observed health effects in humans. This work meets the needs ofthe proposed specific aims by exploring the mechanistic causes cardiovascular health effects observed during exposure to aged or fresh organic carbon aerosol in sensitive animal models and by investigating the role of combustion generated Ni-rich particles on cardiopulmonary injury in animal models. These aims fit within the broader mission of NIH by identifying biological effects associated with environmental contaminants. This research involves a series of in-vivo inhalation exposure studies using a murine model of cardiovascular disease. Over the course of this project, 6 sets of ApoE knockout mice will be exposed to a variety of combustion emissions aerosol. Diluted diesel exhaust will be used to mimic environmentally-relevant exposures near busy roadways. This project also includes the introduction of a custom-built photochemical aging chamber to chemically modify aerosol in order to simulate ambient aerosol processing. This improves the inhalation exposure paradigm by improving the environmental relevance of the exposure since most exposures are a composite of fresh emissions with those that are more aged. Prior to exposure, each mouse will be surgically implanted with radio telemetry devices for real time measurement of mouse activity, body temperature, and 2-channel electrocardiogram. Each exposure experiment is expected to occur 5 times per week, 6 hours per day, for 20 days. At the completion of the exposure, a number of biomarker endpoints will be measured. Brionchial lavage fluid will be collected and centrifuged and the supernatant will be analyzed for biochemical indicators of lung injury (total protein and LDH) and inflammatory cytokines.