目的 探讨piRNA-13663072通过调控Bcl-2/Bax-Caspase-3通路抑制同型半胱氨酸（homocysteine，Hcy）诱导小鼠肾足细胞（MPC-5）凋亡。 方法 通过Cbs^+/- 小鼠建立高Hcy血症（HHcy）肾损伤模型，利用RNA-seq筛选肾脏组织中差异表达的piRNAs；以Hcy（80 μmol/L）体外干预MPC-5细胞构建足细胞损伤模型，采用qRT-PCR验证piR-13663072的表达并进行物种保守性分析。通过转染piR-13663072 mimic、构建过表达细胞模型，转染piR-13663072 inhibitor构建沉默细胞模型，采用Western blot检测凋亡相关蛋白（Bax、Caspase-3、Bcl-2）的表达变化，PI染色检测细胞凋亡数，鬼笔环肽染色观察细胞骨架形态。 结果 Hcy干预可显著诱导MPC-5细胞发生凋亡（促凋亡蛋白Bax、Caspase-3表达升高，抗凋亡蛋白Bcl-2表达降低）与骨架损伤。RNA-seq及qRT-PCR验证显示，piR-13663072在HHcy肾损伤的小鼠肾脏和MPC-5细胞中均显著下调，且该piRNA在哺乳动物中呈中等保守。转染piR-13663072 mimic后，piR-13663072水平显著升高，且能够抑制Bax和Caspase-3的表达，促进Bcl-2的表达，同时有效减少Hcy诱导的PI阳性细胞数量，改善细胞骨架损伤。与之相反，转染piR-13663072 inhibitor后，piR-13663072水平显著降低，可促进Bax和Caspase-3的表达，抑制Bcl-2的表达，进一步增加了Hcy诱导的PI阳性细胞数量，加重细胞骨架损伤。 结论 piR-13663072在Hcy诱导的足细胞损伤中表达下调，过表达piR-13663072可通过调控Bcl-2/Bax-Caspase-3通路，有效抑制足细胞凋亡并减轻骨架损伤，发挥足细胞保护作用，而沉默piR-13663072则会加剧上述损伤，该分子有望成为HHcy肾损伤的潜在生物标志物及治疗靶点。

Objective To investigate whether piR-13663072 inhibits homocysteine （Hcy）-induced apoptosis in mouse podocyte cell line-5 （MPC-5） by regulating the Bcl-2/Bax-Caspase-3 signaling pathway. Methods A hyperhomocysteinemia （HHcy）-induced kidney injury model was established using Cbs^+/- mice， and RNA sequencing （RNA-seq） was employed to screen for differentially expressed piRNAs in kidney tissues. An in vitro podocyte injury model was created by treating MPC-5 cells with Hcy （80 μmol/L）. The expression of piR-13663072 was verified by quantitative real-time PCR （qRT-PCR）， and its species conservation was analyzed. An overexpression cell model was constructed through the transfection of cells with a piR-13663072 mimic. A silenced cell model was constructed via the transfection of cells with a piR-13663072 inhibitor. The expression levels of apoptosis-related proteins （Bax， Caspase-3， and Bcl-2） were detected via Western blot. The number of apoptotic cells was assessed by propidium iodide （PI） staining， and cytoskeletal morphology was observed using phalloidin staining. Results Hcy intervention notably induced apoptosis in MPC-5 cells （as evidenced by the elevated expressions of the pro-apoptotic proteins Bax and Caspase-3， and the reduced expression of the anti-apoptotic protein Bcl-2）， accompanied by cytoskeletal disruption. RNA-seq and qRT-PCR validation demonstrated that piR-13663072 was significantly downregulated in both the kidneys of mice with HHcy-induced injury and Hcy-treated MPC-5 cells. Moreover， this piRNA exhibits moderate conservation among mammals. Following transfection with the piR-13663072 mimic， the expression level of piR-13663072 was significantly elevated. Overexpression of piR-13663072 suppressed the expressions of Bax and Caspase-3， promoted the expression of Bcl-2， effectively decreased the number of Hcy-induced PI-positive cells， and alleviated cytoskeletal damage. Conversely， transfection with the piR-13663072 inhibitor markedly decreased the level of piR-13663072， upregulated the expressions of Bax and Caspase-3， inhibited the expression of Bcl-2， further increased the number of Hcy-induced PI-positive cells， and exacerbated cytoskeletal damage. Conclusions The expression of piR-13663072 is down-regulated in Hcy-induced podocyte injury. Overexpression of piR-13663072 can effectively inhibit podocyte apoptosis and attenuate cytoskeletal damage through the regulation of the Bcl-2/Bax-Caspase-3 signaling pathway， thus exerting a protective effect on podocytes. In contrast， silencing of piR-13663072 aggravates the aforementioned injuries. Therefore， this molecule shows promise as a potential biomarker and therapeutic target for HHcy-induced kidney injury.