目的 探讨circ_0001126在同型半胱氨酸（homocysteinemia，Hcy）导致的小鼠肾足细胞（mouse podocyte cell line-5，MPC-5）铁死亡中的作用。 方法 对MPC-5细胞进行体外培养，将细胞分为Control组（0 μmol/L Hcy）、Hcy组（80 μmol/L Hcy），干预细胞48 h后，分别采用Western blot检测谷胱甘肽过氧化物酶4（glutathione peroxidase 4， GPX4）、溶质载体家族7成员11（solute carrier family 7 Member 11， SLC7A11）蛋白的表达，丙二醛（malondialdehyde， MDA）试剂盒测定细胞内MDA水平，谷胱甘肽（glutathione， GSH）检测试剂盒测定细胞内GSH水平，荧光法检测试剂盒观察细胞内Fe²⁺水平；高通量测序筛选对照组及Hcy组足细胞中特异性环状RNA（circular RNA， circRNA），并以定量逆转录聚合酶链式反应（quantitative Reverse Transcription Polymerase Chain Reaction， qRT-PCR）验证。生物信息学预测染色体位置及保守性。转染si-circ_0001126及其阴性对照（si-NC）后，Western blot及qRT-PCR分别检测GPX4、SLC7A11蛋白及其mRNA表达情况，丙二醛试剂盒测定细胞内MDA水平，GSH检测试剂盒测定细胞内GSH水平，荧光法检测试剂盒观察细胞内Fe²⁺水平。 结果 与Control组相比，Hcy组中铁死亡相关蛋白GPX4、SLC7A11表达降低（P < 0.001），Fe²⁺、MDA表达水平升高（P < 0.001），而GSH水平降低（P < 0.001）；高通量测序发现Hcy组中共有12个表达差异的circRNAs，其中上调的8个，下调的4个，根据|log₂foldchange|（≥ 2）和P值（P < 0.05），筛选出circ_0001126，qRT-PCR验证其Hcy组中表达上调（P < 0.001），与测序结果一致。UCSC Genome Browser Gateway和circbase分析发现circ_0001126主要位于chr3：51659420-51660998，由Maml3基因第2外显子环化形成且具有高度保守性。转染si-circRNAs，发现si-circ_0001126-309干扰效率最佳（P < 0.001）。与Hcy + si-NC组相比，Hcy + si-circ_0001126组铁死亡相关蛋白GPX4、SLC7A11表达升高（P < 0.001），Fe²⁺、MDA表达水平降低（P < 0.001），而GSH水平升高（P < 0.001）。 结论 circ_0001126在Hcy处理的MPC-5细胞中显著增高，降低其表达可抑制Hcy引起的MPC-5细胞铁死亡。

Objective To explore the role of circ_0001126 in homocysteine （Hcy）-induced ferroptosis of Mouse Podocyte Cell line-5 （MPC-5） cells. Methods MPC-5 cells were cultured in vitro and divided into a control group （0 μmol/L Hcy） and an Hcy group （80 μmol/L Hcy）. After 48 hours of cell intervention， the expressions of glutathione peroxidase 4 （GPX4） and solute carrier family 7 member 11 （SLC7A11） proteins were detected by Western blot. The levels of malondialdehyde （MDA） and glutathione （GSH） were measured using a kit， and the level of Fe2? was observed using a fluorescence assay kit. High-throughput sequencing was employed to screen specific circular RNA （circRNA） in podocytes from the control group and the Hcy group， and quantitative reverse transcription polymerase chain reaction （qRT-PCR） was used for validation. Bioinformatics was used to predict chromosome location and conservation. After transfection with si-circ_0001126 and its negative control （si-NC）， the expressions of GPX4 and SLC7A11 proteins and their mRNAs were detected by Western blot and qRT-PCR， respectively. The intracellular MDA level was measured by a malondialdehyde assay kit， the intracellular GSH level was measured by a GSH assay kit， and the intracellular Fe2? level was observed by a fluorescence assay kit. Results Compared with the Control group， the Hcy group exhibited a significant decrease in the expression of ferroptosis related proteins GPX4 and SLC7A11（P < 0.001）， a notable increase in the expression levels of Fe²⁺ and MDA（P < 0.001）， and a marked decrease in GSH levels（P < 0.001）； High throughput sequencing revealed a total of 12 circRNAs with differential expression in the Hcy group， including 8 up-regulated and 4 down-regulated. Based on |log₂foldchange| （≥ 2） and P value （P < 0.05）， circ_0001126 was screened out， and qRT-PCR was used to verify its upregulation in the Hcy group， which is consistent with the sequencing results（P < 0.001）. Analysis using the UCSC Genome Browser Gateway and circbase showed that circ_0001126 is primarily located at chr3：51659420-51660998， formed by the cyclization of the second exon of the Maml3 gene and is highly conserved. Transfection of si-circRNAs demonstrated that si-circ_0001126-309 had the optimal interference efficiency （P < 0.001）. Compared with the Hcy + si-NC group， the Hcy + si-circ_0001126 group showed a significant increase in the expression of ferroptosis-related proteins GPX4 and SLC7A11 （P < 0.001）， a notable decrease in Fe²⁺ and MDA expression levels（P < 0.001）， and an marked increase in GSH levels（P < 0.001）. Conclusion circ_0001126 shows a significant up-regulation in MPC-5 cells treated with Hcy， and down-regulating its expression can inhibit Hcy-induced ferroptosis in MPC-5 cells.