Abstract: Objective　To explore the molecular mechanism of naringenin in preventing and treating insulin resistance in rats with polycystic ovary syndrome (PCOS) based on the aspect of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway. Methods　SD rats were injected with dehydroepiandrosterone subcutaneously on the back daily to establish a PCOS model. The model rats were randomly divided into the model group, the naringenin group, the PI3K inhibitor group, and the naringenin+PI3K inhibitor group, with 15 rats in each group. At the same time, 15 SD rats were subcutaneously injected with oil 2 mL/kg on the neck and back, and they were used as the normal control group. The levels of blood glucose, insulin, blood lipids, and reproductive hormones were detected in each group. The morphology of ovary was observed with HE staining. The positive expression of p-PI3K was detected with immunohistochemical method. The protein expression of PI3K/AKT pathway phosphorylated protein, and pathway related protein-insulin receptor substrate-1 (IRS-1), glycogen synthase-3β (GSK-3β), glucose transporter factor-4 (GLUT4), phosphatase and tensin homologue deleted on chromosome 10 (PTEN) were detected with Western blot assay. Results　Compared with the normal control group, the ovarian tissue of the model group showed symptoms of pathological damage such as follicular cystic dilatation, decreased corpus luteum number and granulosa cell layer, and increased atretic follicles, increased levels of blood lipid and blood sugar, increased insulin resistance, and disordered secretion of reproductive hormones, decreased PI3K/AKT pathway phosphorylated proteins and pathway-related proteins IRS-1, GSK-3β phosphorylated protein and GLUT4 protein expression, and increased expression of PTEN protein (P＜0.05). Naringenin could reduce pathological damage such as cystic dilatation of follicles, promote PI3K/AKT pathway phosphorylated proteins and pathway-related proteins IRS-1, GSK-3β phosphorylated protein and GLUT4 protein expression, improve the disorder of reproductive hormone secretion, reduce insulin resistance, blood glucose and blood lipid levels and PTEN protein expression (P＜0.05). PI3K inhibitors could attenuate the above effects of naringenin (P＜0.05). Conclusion　Naringenin can promote the activation of PI3K/AKT pathway, reduce blood glucose and blood lipid levels and insulin resistance, and improve reproductive hormone disorders and ovarian polycystic changes in PCOS rats.

Key words: polycystic ovary syndrome, phosphatidylinositol 3-kinases, protein kinases, glycogen synthase kinase 3 beta, PTEN phosphohydrolase, glucose transporter type 4, insulin receptor substrate proteins, Naringenin, PI3K/AKT pathway