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.
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。