目的:探讨穿心莲内酯对脓毒症大鼠急性肾损伤铁死亡的影响及作用机制。 方法:采用盲肠结扎穿孔（cecal ligation and puncture， CLP）的方法制备复制脓毒症急性肾损伤（sepsis‑associated acute kidney injury， S‑AKI）模型。将40只大鼠随机分为5组，假手术（Sham）组、脓毒症急性肾损伤（CLP）组、脓毒症+二甲亚砜（CLP+DMSO）组、穿心莲内酯（AG）组、铁死亡抑制剂（Fer‑1）组。通过H&E染色、血肌酐（CRE）和尿素氮（BUN）检测观察大鼠肾脏损伤程度；试剂盒检测氧化应激指标谷胱甘肽（GSH）和丙二醛（MDA）的表达以及铁代谢指标Fe³⁺的变化；免疫荧光检测4‑羟基壬烯醛（4‑hydroxynon‑enal，4‑HNE）表达；qRT‑PCR检测铁死亡通路中SLC7A11和GPX4 mRNA表达情况； Western blot检测通路蛋白SLC7A11、GPX4以及铁蛋白（Ferritin）的表达。 结果:与CLP组相比，AG组肾损伤明显减轻， MDA、GSH和Fe³⁺的表达明显降低，氧化应激和铁的积累减少， SLC7A11、GPX4的蛋白和mRNA的表达上调，而Ferritin蛋白表达下调（P<0.05）。 结论:AG可减轻脓毒症大鼠急性肾损伤，其机制可能与调控SLC7A11/GPX4介导的抗铁死亡及减轻氧化应激和脂质过氧化机制有关。

Objective:To explore the effect and mechanism of action of Andrographolide on ferroptosis in sepsis‑associated acute kidney injury in rats. Methods:In this study， a replica sepsis‑associated acute kidney injury （S‑AKI） model was prepared by cecal ligation and puncture （CLP）. A total of 40 rats were randomly divided into five groups， the Sham group， the CLP group， the sepsis+dimethyl sulfoxide （CLP+DMSO） group， the AG group， and the ferroptosis inhibitor （Fer‑1） group. The degree of kidney injury in rats was observed by H&E staining， blood creatinine （CRE） and urea nitrogen （BUN） test； The expression levels of malondialdehyde （MDA） and glutathione （GSH）， indicators of oxidative stress， as well as changes in Fe³⁺， an indicator of iron metabolism， were detected by the kit； The expression level of 4‑hydroxynon‑enal （4‑HNE） was detected by immunofluorescence； And qRT‑PCR was used to detect the expression of SLC7A11 and GPX4 mRNA in the classical pathway of ferroptosis； Western blot was used to detect the expression levels of pathway proteins SLC7A11， GPX4 and Ferritin. Results:Compared to the CLP group， the AG group renal injury was significantly attenuated， the expression levels of MDA， GSH and Fe³⁺ was significantly decreased， oxidative stress and iron accumulation was reduced， the expression levels of protein and mRNA of SLC7A11 and GPX4 was up‑regulated， and the expression level of Ferritin protein was down‑regulated （P<0.05）. Conclusion:AG attenuates sepsis‑associated acute kidney injury in septic rats， and the mechanism may be related to the regulation of SLC7A11/GPX4‑mediated anti‑ferroptosis and attenuation of oxidative stress and lipid peroxidation mechanisms.

R285.5

国家自然科学基金（81860336）；兵团指导性项目（2023ZD007）