荆 忻,罗彩琴

目的：深入探究褪黑素通过调控p53通路诱导铁死亡减轻脓毒症心肌损伤的具体机制。方法：选取成年C57BL/6小鼠，随机分为对照组、脓毒症组、脓毒症+褪黑素组、脓毒症+褪黑素+p53抑制剂组。通过腹腔注射致死量脂多糖（LPS，10mg/kg）建立脓毒症小鼠模型，褪黑素（10mg/kg）经腹腔注射给予相应组小鼠。结果：褪黑素处理显著改善脓毒症小鼠心脏功能，EF值升高，LVIDs和LVIDd恢复正常；抑制p53激活，其下游靶基因p21、Bax和Caspase-3激活水平下降；调节铁死亡相关标志物，GPX4和xCT表达提高，铁死亡相关蛋白Ferroportin表达降低，脂质过氧化物和铁离子含量减少。结论：褪黑素通过抑制p53激活，增强xCT表达，抑制铁死亡，显著缓解脓毒症引起的心肌损伤，具有潜在临床应用价值。

褪黑素；脓毒症；心肌损伤；p53；铁死亡；xCT

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