The Expression Of Ovarian Local Regulator In Polycystic Ovary Syndrome Rats And The Effect Of Metformin On Its

Objective:Using the polycystic ovary syndrome(PCOS) rats model induced by letrozole as the study object, to investigate the relationship among tumor necrosis factor -α(TNF-α), basic fibroblast growth factor(bFGF),connective tissue growth factor(CTGF) and ovary pathology change in PCOS rats and to investigate the effects of metformin on PCOS rats and to analyze the possible mechanism.Methods:Forty female Wistar rats of six weeks age were randomly divided into model group(30 cases) and control group(10 cases). Set up an animal model by using the non - steroidal aromatase inhibitor– Letrozole. During this period, vaginal smears were collected daily for estrus cycle determonation. After completing the PCOS rats model, the model group rats were drawed ten randomly, according to vaginal smears results, serum hormone level and ovary tissue polycystic to assess model effect, when the success rates are over 80%,the model group remain rats were randomly divided into metformin treatment group(treatment group) and placebo group(PCOS group),ten for each group.The treatment group was administered metformin at concentration of 300mg/kg p.o.dissolved in distilled water,while PCOS group and control group was administered distilled water p.o., after fourteen days, all the rats are performed oral glucose tolerance test (OGTT). the level of fasting blood glucose(FPG),One-hour postprandial blood glucose (1hPG)and Two-hour postprandial blood glucose (2hPG)are determined using a blood glucose meter. The level of serum luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), testoterone(T) and fasting insulin(FIN) was detected by radioimmunoassay(RIA). The ovary tissue of every group rats underwent paraffin imbedding, microtome section, HE staining and then observed their pathohistology by lighter microscope. The expression of TNF-α, bFGF and CTGF in every group ovary were detected and evaluated by immunohistochemistry and image analysis system.Results:1.The estrus cycles of model group showed irregular change, which indicating the rats had no ovulation.2.The average ovary weight of PCOS group is higher than control group and treatment group(P<0.05).Ovary surface is pale, has larger volume and is seen many the saccade expansion follicle. 3.Histologic detection of ovaries: In PCOS group, it can be seen saccular dilatation follicle, the decreased number of corpora lutea, a thin layer of granulosa cells, the puff alignment granulosa cells and a thick layer of theca cells. In treatment group,it can be seen increased granular cell layer, decreased theca cell layer and increased corpora lutea.4.OGTT and fasting insulin level: The values of FIN,FPG,1hPG and 2hPG in PCOS group are higher than those of the control group(P <0.05), The values of FIN,FPG,1hPG and 2hPG in treatment group are lower than those of the PCOS group(P <0.05).5.Detection of the serum gonadal hormone level: The values of T and LH in PCOS group are higher than those of the control group(P <0.05), The values of E2 and FSH in PCOS group are lower than those of the control group(P <0.05). The values of T and LH in treatment group are lower than those of the PCOS group(P <0.05), The values of E2 and FSH in treatment group are higher than those of the PCOS group(P <0.05).6.Expression of local regulators in the ovary: The expression of TNF-α, bFGF and CTGF in granular cells was significantly higher in PCOS group than in control group (P<0.05), The expression of TNF-α,bFGF and CTGF in granular cells was significantly lower in treatment group than in PCOS group (P<0.05). The expression of TNF-α,bFGF and CTGF in theca cells was significantly higher in PCOS group than in control group (P<0.05), The expression of TNF-α,bFGF and CTGF in theca cells was significantly lower in treatment group than in PCOS group (P<0.05).Conclusions:1. Letrozole-induced model in rats can be served as the ideal model of PCOS, which has high dependability.2. The expression of TNF-α, bFGF and CTGF in the ovary is highly correlated with the pathogenesy of PCOS.3. Metformin could regulate the expression of the TNF-αin rats ovary and the endocrine function to treat PCOS.