滴注20纳米柠檬酸盐包被的纳米银后发生的心脏缺血再灌注损伤
Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver.
作者信息
Holland N A, Becak D P, Shannahan Jonathan H, Brown J M, Carratt S A, Winkle Lsv, Pinkerton K E, Wang C M, Munusamy P, Baer Don R, Sumner S J, Fennell T R, Lust R M, Wingard C J
机构信息
Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, USA.
出版信息
J Nanomed Nanotechnol. 2015 Nov;6(Suppl 6). doi: 10.4172/2157-7439.S6-006. Epub 2015 Oct 1.
BACKGROUND
Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano-scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been reported to date. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of carbon-based nanomaterials. We hypothesized pulmonary exposure to Ag core AgNP induces a measureable increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and is associated with depressed coronary constrictor and relaxation responses. Secondarily, we addressed the potential contribution of silver ion release on AgNP toxicity.
METHODS
Male Sprague-Dawley rats were exposed to 200 μl of 1 mg/ml of 20 nm citrate-capped Ag core AgNP, 0.01, 0.1, 1 mg/ml Silver Acetate (AgAc), or a citrate vehicle by intratracheal (IT) instillation. One and 7 days following IT instillation the lungs were evaluated for inflammation and the presence of silver; serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and coronary artery reactivity were assessed.
RESULTS
AgNP instillation resulted in modest pulmonary inflammation with detection of silver in lung tissue and alveolar macrophages, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17α, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Silver within lung tissue was persistent at 7 days post IT instillation and was associated with an elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. AgAc resulted in a concentration dependent infarct expansion and depressed vascular reactivity without marked pulmonary inflammation or serum cytokine response.
CONCLUSIONS
Based on these data, IT instillation of AgNP increases circulating levels of several key cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.
背景
银纳米颗粒（AgNP）因其抗菌特性而备受关注，成为应用最为广泛的纳米级材料之一。然而，迄今为止，尚未有关于与暴露相关的任何潜在心血管损伤的报道。我们之前已经证明，经气管内（IT）滴注碳基纳米材料后心肌梗死范围会扩大。我们推测，肺部暴露于银核AgNP会导致循环细胞因子出现可测量的增加、心脏缺血再灌注（I/R）损伤范围扩大，并且与冠状动脉收缩和舒张反应减弱有关。其次，我们探讨了银离子释放对AgNP毒性的潜在影响。
方法
将雄性Sprague-Dawley大鼠经气管内（IT）滴注200μl 1mg/ml的20nm柠檬酸盐包被的银核AgNP、0.01、0.1、1mg/ml的醋酸银（AgAc）或柠檬酸盐载体。IT滴注后1天和7天，评估肺部的炎症情况以及银的存在；分析血清中选定细胞因子的浓度；评估心脏I/R损伤和冠状动脉反应性。
结果
与载体处理的大鼠相比，滴注AgNP后导致轻度肺部炎症，在肺组织和肺泡巨噬细胞中检测到银，血清细胞因子升高：粒细胞集落刺激因子（G-CSF）、巨噬细胞炎性蛋白-1α（MIP-1α）、白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、白细胞介素-13（IL-13）、白细胞介素-10（IL-10）、白细胞介素-18（IL-18）、白细胞介素-17α（IL-17α）、肿瘤坏死因子α（TNFα）和调节激活正常T细胞表达和分泌因子（RANTES），I/R损伤范围扩大，IT滴注后1天冠状动脉血管反应性降低。IT滴注后7天，肺组织中的银持续存在，并与细胞因子升高有关：IL-2、IL-13和TNFα以及I/R损伤范围扩大。AgAc导致梗死范围呈浓度依赖性扩大，血管反应性降低，而无明显肺部炎症或血清细胞因子反应。
结论
基于这些数据，IT滴注AgNP会增加几种关键细胞因子的循环水平，这可能通过血管反应性受损导致I/R损伤持续扩大。
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