β-谷甾醇通过调控CYP17A1/CYP19A1改善多囊卵巢综合征的作用机制研究

Research on the Mechanism of β-Sitosterol in Improving Polycystic Ovary Syndrome by Regulating CYP17A1/CYP19A1 Expression

摘要: 多囊卵巢综合征(PCOS)是一种常见的内分泌代谢性疾病，以高雄激素血症、排卵障碍和卵巢多囊样改变为主要特征。本研究基于网络药理学方法从52个治疗PCOS的中药方剂中筛选出高频活性成分β-谷甾醇，并探讨其通过调控CYP17A1和CYP19A1表达改善PCOS的作用机制。通过构建DHEA诱导的PCOS小鼠模型，以灌胃的方法在给予β-谷甾醇干预后，检测小鼠体重、动情周期、卵巢组织形态及卵巢组织中CYP17A1、CYP19A1和AR的表达变化。结果显示，β-谷甾醇可明显改善PCOS小鼠的体重、恢复动情周期、减少囊状卵泡数量，显著下调卵巢组织中CYP17A1、AR的mRNA和蛋白表达水平，并上调CYP19A1的mRNA和蛋白表达水平。本研究首次系统揭示β-谷甾醇通过调控类固醇激素合成通路关键酶表达改善PCOS的分子机制，为中医药治疗PCOS提供新的理论依据和潜在治疗策略。

Abstract: Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovarian morphology. Based on network pharmacology analysis of 52 traditional Chinese medicine prescriptions for PCOS, this study identified β-sitosterol as a high-frequency active component and investigated its mechanism in improving PCOS by regulating the expression of CYP17A1 and CYP19A1. A DHEA-induced PCOS mouse model was established, and after intervention with β-sitosterol via oral gavage, changes in body weight, estrous cycle, ovarian morphology, and the expression levels of CYP17A1, CYP19A1, and AR in ovarian tissues were measured. The results showed that β-sitosterol significantly improved body weight, restored the estrous cycle, reduced the number of cystic follicles, markedly downregulated the mRNA and protein expression levels of CYP17A1 and AR in ovarian tissues, and upregulated the mRNA and protein expression levels of CYP19A1. This study systematically reveals for the first time the molecular mechanism by which β-sitosterol ameliorates PCOS by regulating key enzymes in the steroid hormone synthesis pathway, providing a new theoretical basis and potential therapeutic strategy for traditional Chinese medicine in treating PCOS.