Objective: To explore the role and molecular mechanism of peroxiredoxin 1 (PRDX1) in hypertension-induced endothelial dysfunction. Methods: (1) Bioinformatics analysis: A total of 40 C57BL/6J mice aged 8-10 weeks (20-25 g) were randomly divided into the saline group and angiotensin Ⅱ (AngⅡ, 0.8 mg·kg⁻¹·d⁻¹) group, with 20 mice in each group. After 4 consecutive weeks of intervention, mice were sacrificed, and thoracic aortic tissues were collected for transcriptome sequencing. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on differentially expressed genes. (2) Cell experiments: Human umbilical vein endothelial cells (HUVECs) were divided into the control group (endothelial cell culture medium) and the AngⅡ intervention group (medium containing 10-⁶ mol/L AngⅡ). Wound healing assay, cell adhesion assay, and Transwell assay were used to assess cell migration and adhesion. Lentiviral or small interfering RNA (siRNA) transfection was performed to achieve PRDX1 overexpression and knockdown, respectively. The overexpression experiment was divided into the LV-NC (negative control lentivirus) group, Ang Ⅱ+LV-NC group, LV-PRDX1 (PRDX1 overexpression lentivirus) group and Ang Ⅱ+LV-PRDX1 group. The knockdown experiment was divided into the NC-siRNA (negative control siRNA) group, si-PRDX1 group, NC-siRNA+rapamycin (50 nmol/L) group and si-PRDX1+rapamycin group. Immunofluorescence staining was applied to detect intracellular reactive oxygen species level. Quantitative reverse transcription-polymerase chain reaction was used to detect the mRNA expression levels of PRDX1 and mammalian target of rapamycin (mTOR). Western blot was adopted to determine the total protein and phosphorylation levels of PRDX1, mTOR, p70 ribosomal S6 kinase (p70S6K) 1 and endothelial nitric oxide synthase (eNOS). Co-immunoprecipitation assay was used to verify the protein interaction between PRDX1 and mTOR. Nitrate reductase method was used to measure cellular nitric oxide (NO) content. (3) Animal experiments: Forty C57BL/6J mice aged 8-10 weeks (20-25 g) were used to construct the PRDX1 overexpression model via adeno-associated virus serotype 9 (AAV9) vector. Mice were assigned into 4 groups with 10 animals per group: saline+AAV9-GFP (empty vector) group, saline+AAV9-PRDX1 (recombinant virus) group, AngⅡ+AAV9-GFP group, and AngⅡ+AAV9-PRDX1 group. Systolic blood pressure and diastolic blood pressure of mice in each group were dynamically monitored at day 0, 7, 14, 21 and 28 after modeling. Plasma NO level was detected by the nitrate reductase method. After sacrifice, isolated thoracic aortic tissues were subjected to morphological and pathological staining analysis, and a microvascular tension measurement system was used to evaluate the acetylcholine-mediated endothelium-dependent vasodilation function. Results: (1) Bioinformatics analysis: Transcriptome sequencing revealed that numerous differentially expressed genes were identified in the thoracic aorta of mice in the AngⅡ group compared with the saline group. These genes were mainly enriched in biological processes closely associated with oxidative stress, such as reactive oxygen species metabolism and oxidative phosphorylation regulation. (2) Cell experiments: Compared with the control group, HUVECs in the AngⅡ intervention group presented decreased protein and mRNA levels of PRDX1, as well as elevated phosphorylation levels of mTOR and p70S6K1 (all P<0.05). Compared with the LV-NC group, the LV-PRDX1 group showed higher PRDX1 mRNA expression, lower reactive oxygen species levels, enhanced cell migration and adhesion capacities, and increased NO content (all P<0.05). In contrast with the AngⅡ+LV-NC group, the AngⅡ+LV-PRDX1 group exhibited reduced phosphorylation levels of mTOR and p70S6K1 and increased eNOS phosphorylation level (all P<0.05). In addition, relative to the NC-siRNA group, the si-PRDX1 group had higher reactive oxygen species levels and elevated phosphorylation of mTOR and p70S6K1, accompanied by decreased NO content, reduced eNOS phosphorylation, and weakened cell migration and adhesion abilities (all P<0.05). Compared with the si-PRDX1 group, the above abnormal changes were partially reversed in the si-PRDX1+rapamycin group (all P<0.05). Co-immunoprecipitation assay confirmed a protein interaction between PRDX1 and mTOR. (3) Animal experiments: In comparison with the saline+AAV9-GFP group, the AngⅡ+AAV9-GFP group had higher systolic and diastolic blood pressure, lower plasma NO level, thicker thoracic aortic media, increased collagen deposition, disordered arrangement of elastic fibers, and impaired endothelium-dependent vasodilation in response to acetylcholine (all P<0.05). Notably, the AngⅡ+AAV9-PRDX1 group showed lower systolic and diastolic blood pressure, alleviated pathological damage of the thoracic aorta, improved endothelium-dependent vasodilation function, and higher plasma NO level than the AngⅡ+AAV9-GFP group (all P<0.05). Conclusion: PRDX1 can inhibit the excessive activation of the mTOR/p70S6K signaling pathway by scavenging reactive oxygen species and promoting NO production, thereby regulating eNOS activity and ameliorating endothelial dysfunction and vascular injury under hypertensive conditions. Targeted regulation of the PRDX1/ROS/mTOR/p70S6K signaling axis is expected to provide a novel therapeutic target and intervention strategy for the prevention and treatment of hypertensive vascular diseases. 目的： 探讨过氧化物氧化还原蛋白1（PRDX1）在高血压内皮功能障碍中的作用和分子机制。 方法： （1）生物信息学分析：选取8~10周龄C57BL/6J小鼠（体重20~25 g）40只，随机分为生理盐水组和血管紧张素Ⅱ（AngⅡ，0.8 mg·kg⁻¹·d⁻¹）组，每组20只，连续干预4周后处死小鼠并取胸主动脉组织进行转录组测序，对差异基因进行基因本体功能注释及京都基因与基因组百科全书通路富集分析。（2）细胞实验：选取人脐静脉内皮细胞（HUVECs），分为对照组（内皮细胞培养基）和AngⅡ干预组（含10-6mol/L AngⅡ培养基），采用划痕实验、黏附实验和Transwell实验检测细胞迁移、黏附能力。对HUVECs分别转染慢病毒或小干扰RNA（siRNA）实现PRDX1的过表达与敲低：过表达实验分为LV-NC（阴性对照慢病毒）组、AngⅡ+LV-NC组、LV-PRDX1（PRDX1过表达慢病毒）组和AngⅡ+LV-PRDX1组；敲低实验分为NC-siRNA（阴性对照siRNA）组、si-PRDX1组、NC-siRNA+雷帕霉素（50 nmol/L）组和si-PRDX1+雷帕霉素组；采用免疫荧光染色检测细胞活性氧水平，采用定量逆转录聚合酶链式反应检测PRDX1、哺乳动物雷帕霉素靶蛋白（mTOR）等信使RNA（mRNA）表达水平，Western blot法检测PRDX1、mTOR、p70核糖体S6激酶（p70S6K）1、内皮型一氧化氮合酶（eNOS）总蛋白与磷酸化水平，采用免疫共沉淀实验检测PRDX1与mTOR的蛋白相互作用，采用硝酸还原酶法检测细胞一氧化氮（NO）含量。（3）动物实验：选取8~10周龄C57BL/6J小鼠（体重20~25 g）40只，采用腺相关病毒血清型9（AAV9）载体构建PRDX1基因过表达模型，共设4组，每组10只：生理盐水+AAV9-GFP（空载病毒）组、生理盐水+AAV9-PRDX1（重组病毒）组、AngⅡ+AAV9-GFP组、AngⅡ+AAV9-PRDX1组。于造模后第0、7、14、21、28天动态监测各组小鼠尾动脉收缩压与舒张压，采用硝酸还原酶法检测小鼠血浆NO水平；处死小鼠后对离体主动脉进行组织形态学及病理学染色分析，并采用微血管张力测定系统评估血管对乙酰胆碱的内皮依赖性舒张功能。 结果： （1）生物信息学分析：转录组测序结果显示，与生理盐水组相比，AngⅡ组小鼠胸主动脉组织中存在大量差异表达基因，主要富集于活性氧代谢、氧化磷酸化调控等与氧化应激密切相关的生物学过程。（2）细胞实验：与对照组相比，AngⅡ干预组HUVECs中PRDX1蛋白及mRNA水平均较低，mTOR及p70S6K1磷酸化水平较高（P均<0.05）。与LV-NC组相比，LV-PRDX1组HUVECs中PRDX1 mRNA表达水平较高、活性氧水平较低，细胞迁移和黏附能力均较强，NO含量也较高（P均<0.05）；与AngⅡ+LV-NC组相比，AngⅡ+LV-PRDX1组HUVECs中mTOR和p70S6K1磷酸化水平较低，eNOS磷酸化水平较高（P均<0.05）。此外，与NC-siRNA组相比，si-PRDX1组HUVECs中活性氧水平、mTOR及p70S6K1磷酸化水平较高，NO含量、eNOS磷酸化水平较低，细胞迁移和黏附能力较弱（P均<0.05）；与si-PRDX1组相比，si-PRDX1+雷帕霉素组HUVECs上述改变均得到部分逆转（均P<0.05）。免疫共沉淀实验表明，PRDX1与mTOR存在蛋白相互作用。（3）动物实验：与生理盐水+AAV9-GFP组相比，AngⅡ+AAV9-GFP组小鼠收缩压和舒张压较高，血浆NO水平较低，胸主动脉中膜较厚、胶原沉积增加、弹性纤维排列紊乱，对乙酰胆碱的内皮依赖性舒张反应较弱（P均<0.05）；而AngⅡ+AAV9-PRDX1组小鼠收缩压和舒张压均低于AngⅡ+AAV9-GFP组，上述胸主动脉病理损伤程度较轻，同时对乙酰胆碱的内皮依赖性舒张反应较强，血浆NO水平较高（P均<0.05）。 结论： PRDX1可通过清除活性氧、促进NO生成，抑制mTOR/p70S6K信号通路过度激活，进而调控eNOS活性，改善高血压状态下的内皮功能障碍与血管损伤；靶向调控PRDX1/活性氧/mTOR/p70S6K信号轴有望为高血压血管病变的防治提供新靶点与干预策略。.