目的：探讨阻断雄激素受体（AR）信号通路在男性胸主动脉夹层（TAD）发生中的作用及其分子机制。方法：在TAD临床、动物模型和原代细胞中，通过实时定量PCR和免疫印迹检测AR基因及其下游靶基因FKBP5表达水平。在TAD动物模型分离得到的原代细胞中通过免疫荧光检测AR表达。在TAD动物模型中通过免疫组织化学检测GPX4表达。在血管平滑肌细胞（VSMC）中阻断AR信号通路，通过生化试剂盒分析氧化应激和铁死亡相关标志物变化。利用荧光素酶报告基因、染色质免疫共沉淀及核实时转录分析技术，验证AR信号通路对铁死亡关键抑制基因长链脂酰辅酶A合成酶3(ACSL3)的转录调控作用；通过影像学和组织学方法评估动物模型AR信号通路阻断对TAD发生的影响。结果：与正常主动脉组织相比，男性TAD病人和雄性小鼠TAD模型中VSMC的AR及其靶基因FKBP5表达显著降低。阻断AR信号通路可下调小鼠TAD模型VSMC中铁死亡抑制剂谷胱甘肽过氧化物酶4（GPX4）的表达以诱导TAD形成和破裂。阻断AR信号通路诱导VSMC中氧化应激和铁死亡相关标志物的表达。进一步研究表明，AR通过结合ACSL3启动子区并促进其转录，从而抑制VSMC铁死亡；过表达ACSL3可逆转AR阻断诱导的铁死亡。动物实验显示，阻断AR信号通路促进胸主动脉管腔扩张、弹性纤维断裂，最终导致TAD发生。结论：AR信号通路通过转录激活ACSL3抑制VSMC铁死亡，其功能缺失可导致主动脉壁弹性纤维断裂，进而促进TAD发生发展。

Objective To investigate the impact of blocking androgen receptor (AR) signaling pathway in the pathogenesis of male thoracic aortic dissection (TAD) and to uncover its molecular mechanisms. Methods In TAD clinical samples, animal models and primary cells, real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting were used to detect the expression levels of AR and its pathway target gene FKBP5. Immunofluorescence was used to detect AR expression in primary cells isolated from TAD animal models. Immunohistochemistry was used to detect GPX4 expression in TAD animal models. In vascular smooth muscle cells (VSMCs), the AR signaling pathway was blocked to detect changes in oxidative stress and ferroptosis-related markers using biochemical assays. Luciferase reporter gene, chromatin immunoprecipitation, and nuclear run-on real-time transcription analysis were used to verify the transcriptional regulation of the key ferroptosis inhibitor gene long-chain acyl-CoA synthetase 3 (ACSL3) by the AR signaling pathway. In animal models, imaging and histological methods were employed to elucidate how the inhibition of the AR signaling pathway promotes the occurrence of TAD. Results Compared with normal aortic tissues, the expression of AR and its pathway target gene FKBP5, was reduced in tissues from male TAD patients and in the aortic VSMCs of male mouse TAD model tissues. Blocking the AR signaling pathway significantly reduced the expression levels of the ferroptosis inhibitor glutathione peroxidase 4(GPX4) in mouse aortic VSMCs, inducing the formation and rupture of TAD. Blocking the AR pathway induced the expression of oxidative stress and ferroptosis-related markers in VSMCs. Further research found that AR bound to the ACSL3 promoter region and promoted its transcription, inhibiting ferroptosis in VSMCs. Overexpression of ACSL3 reversed the ferroptosis induced by AR blockade. Animal experiments showed that blocking the AR signaling pathway promoted thoracic aortic lumen dilation, elastic fiber fragmentation, ultimately leading to TAD occurrence. Conclusions The AR signaling pathway inhibits ferroptosis in VSMCs through transcriptional activation of ACSL3. Loss of its function leads to elastic fiber fragmentation of the aortic wall, thereby promoting the occurrence and development of TAD.