PDF(Pubmed)
Abstract：
BACKGROUND: Long-term exposure of humans to air pollution is associated with an increasing risk of cardiovascular diseases (CVDs). Astaxanthin (AST), a naturally occurring red carotenoid pigment, was proved to have multiple health benefits. However, whether or not AST also exerts a protective effect on fine particulate matter (PM2.5)-induced cardiomyocyte damage and its underlying mechanisms remain unclear.
METHODS: In vitro experiments, the H9C2 cells were subjected to pretreatment with varying concentrations of AST, and then cardiomyocyte injury model induced by PM2.5 was established. The cell viability and the ferroptosis-related proteins expression were measured in different groups. In vivo experiments, the rats were pretreated with different concentrations of AST for 21 days. Subsequently, a rat model of myocardial PM2.5 injury was established by intratracheal instillation every other day for 1 week. The effects of AST on myocardial tissue injury caused by PM2.5 indicating by histological, serum, and protein analyses were examined.
RESULTS: AST significantly ameliorated PM2.5-induced myocardial tissue injury, inflammatory cell infiltration, the release of inflammatory factors, and cardiomyocyte H9C2 cell damage. Mechanistically, AST pretreatment increased the expression of SLC7A11, GPX4 and down-regulated the expression of TfR1, FTL and FTH1 in vitro and in vivo.
CONCLUSIONS: Our study suggest that ferroptosis plays a significant role in the pathogenesis of cardiomyocyte injury induced by PM2.5. AST may serve as a potential therapeutic agent for mitigating cardiomyocyte injury caused by PM2.5 through the inhibition of ferroptosis.
METHODS: In vitro experiments, the H9C2 cells were subjected to pretreatment with varying concentrations of AST, and then cardiomyocyte injury model induced by PM2.5 was established. The cell viability and the ferroptosis-related proteins expression were measured in different groups. In vivo experiments, the rats were pretreated with different concentrations of AST for 21 days. Subsequently, a rat model of myocardial PM2.5 injury was established by intratracheal instillation every other day for 1 week. The effects of AST on myocardial tissue injury caused by PM2.5 indicating by histological, serum, and protein analyses were examined.
RESULTS: AST significantly ameliorated PM2.5-induced myocardial tissue injury, inflammatory cell infiltration, the release of inflammatory factors, and cardiomyocyte H9C2 cell damage. Mechanistically, AST pretreatment increased the expression of SLC7A11, GPX4 and down-regulated the expression of TfR1, FTL and FTH1 in vitro and in vivo.
CONCLUSIONS: Our study suggest that ferroptosis plays a significant role in the pathogenesis of cardiomyocyte injury induced by PM2.5. AST may serve as a potential therapeutic agent for mitigating cardiomyocyte injury caused by PM2.5 through the inhibition of ferroptosis.
摘要：
背景：人类长期暴露于空气污染与心血管疾病（CVD）的风险增加有关。虾青素(AST),一种天然存在的红色类胡萝卜素色素，被证明有多种健康益处。然而,AST是否也对细颗粒物（PM2.5）诱导的心肌细胞损伤具有保护作用及其潜在机制尚不清楚。
方法：体外实验，H9C2细胞用不同浓度的AST进行预处理，建立PM2.5致心肌细胞损伤模型。在不同组中测量细胞活力和铁凋亡相关蛋白的表达。体内实验,用不同浓度的AST预处理大鼠21天。随后，隔天气管滴注1周建立大鼠心肌PM2.5损伤模型。AST对PM2.5所致心肌组织损伤的影响,血清,和蛋白质分析进行了检查。
结果：AST显著改善PM2.5引起的心肌组织损伤，炎性细胞浸润，炎症因子的释放，和心肌细胞H9C2细胞毁伤。机械上,AST预处理在体外和体内增加了SLC7A11，GPX4的表达，并下调了TfR1，FTL和FTH1的表达。
结论：我们的研究表明，铁性凋亡在PM2.5诱导的心肌细胞损伤的发病机制中起着重要作用。AST可作为一种潜在的治疗剂，通过抑制铁中毒减轻PM2.5引起的心肌细胞损伤。
方法：体外实验，H9C2细胞用不同浓度的AST进行预处理，建立PM2.5致心肌细胞损伤模型。在不同组中测量细胞活力和铁凋亡相关蛋白的表达。体内实验,用不同浓度的AST预处理大鼠21天。随后，隔天气管滴注1周建立大鼠心肌PM2.5损伤模型。AST对PM2.5所致心肌组织损伤的影响,血清,和蛋白质分析进行了检查。
结果：AST显著改善PM2.5引起的心肌组织损伤，炎性细胞浸润，炎症因子的释放，和心肌细胞H9C2细胞毁伤。机械上,AST预处理在体外和体内增加了SLC7A11，GPX4的表达，并下调了TfR1，FTL和FTH1的表达。
结论：我们的研究表明，铁性凋亡在PM2.5诱导的心肌细胞损伤的发病机制中起着重要作用。AST可作为一种潜在的治疗剂，通过抑制铁中毒减轻PM2.5引起的心肌细胞损伤。
