Abstract: Objective To establish a rat model of polycystic ovary syndrome with insulin resistance (PCOS-IR) by using letrozole combined with high-fat and high-sugar diet. Methods After one week of adjustable feeding, twenty 6-week-old female SD rats were randomly divided into 2 groups:10 rats as control group, the other 10 as model group. Rats in control group were fed with ordinary diet, while model group with high-sugar and high-fat diet for 28 days. From the 8th day, the rats in model group received 0.4 mL letrozole (1 mg/kg) daily for 21 consecutive days and fed with high-sugar and high-fat diet, while rats in control received 0.4 mL 1% carboxymethyl cellulose solution daily and fed with standard diet. The vaginal smear was examined every morning to observe the vaginal exfoliated cell changes from the 15th day to the end of experiment. After lavage, fasting blood glucose (FBG) was measured from caudal vein. The levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) and fasting insulin (FINS) were measured and the LH/FSH ratio, insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated. The changes of body weight and ovarian histological phenotypes were observed. Results Compared with the control group,the body weight, the levels of FBG, FINS, T, LH, HOMA-IR, and LH/FSH ratio all increased significantly in model group, while the FSH and ISI levels in the model group decreased significantly,the difference were all statistically significant (P<0.01). The vaginal smear showed that the estrus cycle disappeared in the model group. The local ovarian tissue morphology was normal in the control group, while the model group expressed typically polycystic changes. Conclusion Letrozole combined with high-sugar and high-fat diet can successfully induce PCOS-IR rat model with typical polycystic changes, insulin resistance and endocrine abnormality.

Key words: polycystic ovary syndrome, insulin resistance, letrozole, high-sugar and high-fat diet, rat model