为了研究金雀异黄素（Genistein，Gen）通过脂联素（Adiponectin，APN）和视黄醇结合蛋白-4（Retinol Binding Protein 4，RBP4）途径调节多囊卵巢综合征并发胰岛素抵抗（Polycystic Ovary Syndrome-Insulin Resistance，PCOS-IR）大鼠的胰岛素抵抗作用。通过皮下注射脱氢表雄酮（Dehydroepiandrosterone，DHEA）和人绒毛膜促性腺激素（Human Chorionic Gonadotropin，HCG）结合高脂饲料的方法，建立PCOS-IR大鼠模型。大鼠根据体质量随机分为对照组、模型组，Gen-低、中、高剂量组和二甲双胍组，每组8只，连续干预21 d，测定大鼠空腹血糖（Fasting Blood Glucose，FBG）、胰岛素（Fasting Insulin，Fins）、APN、RBP4相关指标水平，检测卵巢组织内APN和RBP4相关基因和蛋白的表达。结果发现，与模型组相比，Gen-中剂量组空腹血糖值显著降低13.95%，Gen-中、高剂量组空腹胰岛素分别降低45.80%、51.80%，Gen-高剂量组胰岛素抵抗指数显著降低57.20%；与模型组比较，Gen-中剂量大鼠血清APN、APPL1水平分别显著提升69.43%、36.57%，Gen-高剂量组RBP4水平显著降低59.01%，Gen-中剂量组PEPCK水平显著下降22.63%；Gen-中、高剂量组卵巢组织APPL1、AMPK、p-AMPK的基因和蛋白表达水平显著提高，RBP4、PEPCK的基因和蛋白表达水平显著降低。研究表明，中、高剂量（20、30 mg/kg）Gen可通过脂联素和RBP4途径有效改善PCOS-IR大鼠的糖代谢和胰岛素抵抗。

A rat model of polycystic ovary syndrome with insulin resistance (PCOS-IR) was established by administering subcutaneous injections of dehydroepiandrosterone (DHEA) and human chorionic gonadotropin (HCG) and a high-fat diet to study the effects of genistein (Gen) on insulin resistance through adiponectin (APN) and retinol binding protein-4 (RBP4) pathways. Rats were randomly divided into the control group, model group, low-, medium-, and high-dose Gen treatment groups, and metformin treatment group according to their body weights. Each group had eight rats. After 21 days of continuous treatment, the levels of Fasting Blood Glucose (FBG), Fasting insulin (Fins), APN, and RBP4 were measured, and the expression of APN- and RBP4-related genes and proteins in the ovarian tissue was analyzed. The results showed that in comparison with the model group, the medium-dose Gen treatment group had a significantly decrease of 13.95% in the FBG. Fins levels of the medium- and high-dose Gen treatment groups decreased by 45.80% and 51.80%, respectively, as compared to the level in the model group. The insulin resistance index of the high-dose group significantly reduced by 57.20%. Serum APN and Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) levels of the medium-dose group were significantly higher by 69.43% and 36.57%, respectively, and RBP4 level of the high-dose group was significantly lower by 59.01% than those in the model group. The level of phosphoenolpyruvate carboxykinase (PEPCK) of the medium-dose group remarkably reduced by 22.63%. The gene and protein expression levels of APPL1, AMP-activated protein kinase (AMPK), and p-AMPK in the ovarian tissue of the medium- and high-dose groups considerably increased, but those of RBP4 and PEPCK significantly decreased. Thus, medium and high doses (20 and 30 mg/kg) of Gen can effectively improve glucose metabolism and insulin resistance in PCOS-IR rats through adiponectin and RBP4 pathways.

国家自然科学基金面上项目（81673170）；黑龙江省科技厅自然基金研究团队项目（TD2020C003）；国家重点研发计划项目（2018YFE0206300）；黑龙江省自然科学基金项目（LH2021H055）