目的  探讨普拉克索治疗不宁腿综合征(restless legs syndrome,RLS)的潜在分子机制，为临床治疗提供依据。 方法  利用DisGeNET、GeneCards、NCBI等数据库筛选RLS与普拉克索相关基因，确定共享基因。通过STRING数据库进行功能富集与蛋白-蛋白网络分析，结合Cytoscape构建Hub基因网络，并在GEO数据库(GSE54839、GSE37171)中验证其表达。采用分子对接与分子动力学模拟评估普拉克索与关键基因的结合稳定性。最终，在维持性血液透析并发RLS患者中结合临床指标评估普拉克索的作用。 结果  生物信息分析结果显示SLC6A3在GEO数据集(GSE54839、GSE37171)中显著上调，分类效能较高(GSE54839：AUC=0.755；GSE54839：AUC=0.606)。分子对接和分子动力学分析显示SLC6A3与普拉克索结合能稳定，动态条件下表现出较强的结构稳定性。在临床队列中，RLS患者血清SLC6A3蛋白相对表达水平与维持性血液透析组[(2.29±0.388)比(1.30±0.422)，t=4.603,P＜0.001]和对照组[(2.29±0.388)比(1.30±0.422)，t=4.603,P＜0.001)]相比升高，与多巴胺水平呈负相关(R ²=0.601，P＜0.001)。普拉克索治疗可改善RLS患者国际不宁腿综合征评分量表(international restless legs syndrome rating scale，IRLS)评分[(15.8±1.67)分比(21.8±4.31)分，t=4.379，P＜0.001]，并调节SLC6A3[给药组(1.64±0.41)比对照组(2.31±0.39)，t=4.112，P＜0.001]及多巴胺[给药组(231.50±13.03)比对照组(195.50±14.09)，t=3.461，P＜0.001]表达水平。 结论  SLC6A3是普拉克索治疗RLS的重要作用靶点，可作为潜在的生物标志物，为RLS的个性化治疗提供新思路。

Objective   To explore the potential molecular mechanisms of pramipexole in the treatment of restless legs syndrome (RLS) and provide a basis for clinical therapy.  Methods   RLS and pramipexole-related genes were screened using DisGeNET, GeneCards, and NCBI databases to identify shared genes. Functional enrichment and protein-protein interaction (PPI) analyses were performed via the STRING database, and a hub gene network was constructed using Cytoscape. The expression of key genes was validated in the GEO datasets (GSE54839, GSE37171). Molecular docking and molecular dynamics simulations were used to assess the binding stability between pramipexole and key genes. Finally, the effects of pramipexole were evaluated in maintenance hemodialysis (MHD) patients with RLS based on clinical indicators.  Results  The bioinformatics analysis shows that SLC6A3 is significantly upregulated in the GEO datasets (GSE54839, GSE37171), with high classification performance (GSE54839: AUC =0.755; GSE37171: AUC =0.606). Molecular docking and molecular dynamics analysis revealed that SLC6A3 binds stably with pramipexole and exhibits strong structural stability under dynamic conditions. In the clinical cohort, the relative serum expression level of SLC6A3 in RLS patients is significantly higher compared to the MHD group [(2.29±0.388) vs. (1.30±0.422), t=4.603, P＜0.0001] and the control group [(2.29±0.388) vs. (1.30±0.422), t=4.603,  P＜0.0001]. It is negatively correlated with dopamine levels (R²=0.601, P＜0.001). Pramipexole treatment significantly improves the IRLS (International Restless Legs Syndrome Rating Scale) score in RLS patients [(15.8±1.67) vs. (21.8 ±4.31), t=4.379, P＜0.001], and modulates the expression levels of SLC6A3 [treatment group (1.64±0.41) vs. control group (2.31±0.39), t=4.112, P＜0.001] and dopamine [treatment group (231.50±13.03) vs.control group (195.50±14.09), t=3.461, P＜0.001].   Conclusion  SLC6A3 is a key therapeutic target of pramipexole for RLS and may serve as a potential biomarker, providing new insights for personalized treatment of RLS.