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目的 探讨腺苷酸激活蛋白激酶(AMPK)对棕榈酸(PA)诱导的大鼠心肌细胞铁死亡的作用及其机制。方法 用PA处理H9c2细胞24h, CCK-8检测PA对细胞活力的影响，通过RT-qPCR和Western blot检测AMPK、Nrf2、HO-1以及铁死亡相关因子的表达变化，并采用探针法检测细胞脂质过氧化物(LPO)水平的变化。进一步用AMPK激动剂AICAR或抑制剂Compound C预处理，评估上述指标变化。同时，利用试剂盒分别检测各组细胞中铁离子、MDA和GSH水平的变化。结果 PA增加细胞LPO含量，降低AMPK、Nrf2、HO-1和铁死亡相关因子SLC7A11、GPX4的蛋白和基因表达水平；然而，AMPK激动剂AICAR预处理逆转PA诱导的细胞损伤，提高细胞GSH,降低MDA和铁水平；相反，AMPK抑制剂Compound C则进一步加剧损伤，降低细胞GSH,增加MDA和铁水平(P<0.05)。结论 PA通过下调AMPK调控Nrf2/HO-1信号通路，从而诱导大鼠心肌细胞铁死亡。
Abstract：Objective To investigate the role of adenylate activated protein kinase(AMPK) and its mechanism on palmitic acid(PA)-induced ferroptosis in rat cardiomyocytes.Methods The H9c2 cells were treated with PA for 24 hours, and the effect of PA on cell viability was detected by CCK-8.The expression levels of AMPK,Nrf2,HO-1,and ferroptosis-related factors were detected by RT-qPCR and Western blot.And the lipid peroxidation level was detected by lipid peroxidation assay kit.Further pretreatment with AMPK agonist AICAR or inhibitor Compound C was performed to evaluate the changes in the above indicators.Meanwhile, iron assay kit, MDA kit and GSH assay kit were utilized to detect the changes in the content of iron ions, MDA and GSH in each group, respectively.Results PA increased the content of LPO and decreased the protein and gene expression levels of AMPK,Nrf2,HO-1,ferroptosis-related factors SLC7A11 and GPX4.However, pretreatment with the AMPK agonist AICAR reversed PA-induced cell damage, increased cellular GSH levels, and decreased MDA and iron levels.In contrast, the AMPK inhibitor Compound C further exacerbated the damage, decreased the cellular GSH level, and increased MDA and iron levels(P<0.05).Conclusion PA induces ferroptosis in rat cardiomyocytes by modulating the Nrf2/HO-1 signaling pathway through down-regulation of AMPK.
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基本信息:
DOI：10.16751/j.cnki.2095-4646.2025031308
中图分类号:R965
引用信息:
[1]凌莉,华玉,季慧敏,等.棕榈酸通过抑制AMPK-Nrf2/HO-1轴诱导大鼠心肌细胞铁死亡[J].湖北科技学院学报(医学版),2025,39(05):380-385+364.DOI:10.16751/j.cnki.2095-4646.2025031308.
基金信息:
糖尿病与血管病变专项项目(2022TNB04); 湖北科技学院科研创新团队项目(2022T01)