Objective: To investigate the effect of metformin on the inflammatory response in polycystic ovary syndrome (PCOS) model rats and its regulatory role in the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway. Methods: Among 50 female SD rats, 40 rats were used to establish a PCOS model via letrozole induction and then randomly divided into the model group and low-, medium-, and high-dose metformin groups (n=10 each). The remaining 10 rats served as the control group. The low-, medium- and high-dose metformin groups were administered metformin via oral gavage at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg, respectively (all at a volume of 5 mL/kg). The control and model groups received 5 mL/kg normal saline via oral gavage. All treatments were administered once daily for four consecutive weeks. The estrous cycle changes were observed. Serum sex hormone levels [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T)] and inflammatory factor levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-18] were measured by enzyme-linked immunosorbent assay (ELISA). Ovarian morphology was examined via hematoxylin and eosin (HE) staining, and ovarian cell apoptosis was assessed via TUNEL staining. The expression levels of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), c-Jun N-terminal protein kinase (JNK), p-JNK, p38 MAPK, p-p38 MAPK, NF-κB p65, and p-NF-κB p65 proteins in ovarian tissues were detected by Western blotting. Results: The estrous cycle was disordered in the model group, while all metformin-treated groups showed improvements, with the most significant improvement observed in the high-dose metformin group. Compared with the control group, the model group exhibited decreased serum levels of FSH and E2, and increased levels of LH, T, inflammatory factors, apoptosis rate, and the expression of p-ERK, p-JNK, p-p38 MAPK and p-NF-κB p65 proteins (all P<0.05). Compared with the model group, all metformin-treated groups demonstrated increased levels of FSH and E2, and decreased levels of LH, T, inflammatory factors, apoptosis rate, and the expression of p-ERK, p-JNK, p-p38 MAPK and p-NF-κB p65 proteins, with the most significant improvements observed in the high-dose metformin group (all P<0.05). Ovarian morphology abnormalities improved in all metformin-treated groups, most notably in the high-dose metformin group. Conclusions: Metformin can improve the estrous cycle, regulate sex hormones, and reduce cell apoptosis in PCOS rats. Its mechanism of action may involve alleviating the inflammatory response by inhibiting the MAPK/NF-κB pathway.
