Study On The Function Of Irisin In The Metabolism Of Polycystic Ovary Syndrome Rat Model

ObjectiveEvaluate the significance of letrozole-induced polycystic ovary syndrome ratmodels; explore the appropriate and suitable letrozole concentration to induce thePCOS rat model; investigate the serum Irisin level of PCOS rats and its relationshipwith serum sex hormones，insulin and insulin resistance; analyse the expression ofFNDC5mRNA in rat gastrocnemius muscle; explore the role of Irisin in pathogenesisof PCOS rats.MethodPartⅠ:To feed6-week female SD rats with different concentrations of letrozole:1.0mg/kg.d and0.5mg/kg.d for21days to built PCOS rat model. And find out thesuitable concentration of letrozole for modeling.PartⅡ:With different interventions,40female SD rats were divided into four groups:normal weight non-PCOS group (n=10), obese non-PCOS group (n=10), normalweight PCOS group (n=10) and obese PCOS group (n=6, after exclude4rats, whichdon’t meet the obese requirements). The HE staining was used to observe the ovarymorphology; serum T, LH and INS levels of each groups were measured byradioimmunoassay technique; fasting blood glucose was measured by glucoseoxidation technique; serum Irisin concentrations were measured by Elisa; Rt-PCRmethod was used to detect FNDC5mRNA (Irisin’s precursor)expression in ratgastrocnemius muscle; analyse and compare indicatiors above of each groups. ResultPartⅠ:1. In letrozole-induced PCOS rat models:①certain sex and endocrine hormoneschanged: T, LH, INS and HOMA-IR wered obviously increased compared to controlgroup (P<0.05).②ovaries of PCOS rats changed: the weight and the volumeincreased. The appearance of ovaries was pale and polycystic; white membranes ofovaries were thicken, there were more immature follicles, less yellow bodies,andthinner layers of granule cells in PCOS rat model. Vaginal smears showed estrouscycle regularity disappeared in PCOS rat model, and all PCOS rats stayed in diestrus.Those changes in PCOS rat models are in line with physiological changes of PCOSpatients.2.Serum T, LH, INS and HOMA-IR levels were higher in high letrozoleconcentration(1mg/kg.d)-induced PCOS rat models than lower letrozoleconcentration(0.5mg/kg.d)models(P<0.05).Vaginal smears showed disappearance ofestrous cycle occurred earlier in PCOS rat models induced by high letrozoleconcentration than lower one.Part Ⅱ:1. Elisa method was used to detect the concentrations of serum Irisn in4groups.The levels of serum Irisin level were higher in non-PCOS groups than PCOS groups(P <0.05). The serum Irisin level of normal weight non-PCOSgroup was higher thanthat of obese non-PCOSgroup (P <0.05), Irisin level was also higher in normal weightPCOS group than obese PCOS group (P <0.05).2.Person correlation analysis showed that: in non-PCOS groups, serum Irisinconcentration had significantly negative correlations with body weight and LEE index(Rw=-0.858， P<0.001； RLEE=-0.885， P<0.001). In PCOS groups, serum Irisinconcentration had significantly negative correlations with body weight, T, LH, INS,HOMA-IR and LEE index,(RW=-0.840，P<0.001；RT=-0.891，P<0.001；RLH=-0.505，P<0.05；RINS=-0.892，P<0.001；RIR=-0.866，P<0.001；RLEE=-0.839，P<0.001). Inboth non-PCOS groups and PCOS groups, the correlations between Irisin and blood glucose were not significant(Rnon-PCOS=-0.131，P=0.581；RPCOS=-0.008，P=0.976).3.In multivariate linear regression analysis: in non-PCOS groups, LEE index wasa meaningful predictive factor for Irisin (β=-0.885, P<0.001); in PCOS groups, INSand T are meaningful predictors for Irisin (β=-0.501, P=0.005).4.Use the technology of Rt-PCR to mesure the expressin of FNDC5mRNA of ratgastrocnemius muscle in4groups,which suggested that in non-PCOS groups, FNDC5mRNA expression were higher, compared with PCOS groups(P<0.05). Theexpression of FNDC5mRNA was higher in normal weight non-PCOS group than inobese non-PCOS group (P<0.05). It was also higher in normal weight PCOS groupthan obese PCOS group (P<0.05).Conclusion1.The letrozole-induced PCOS rat model is an appropriate and suitable one tostudy the pathophysiology and endocrine changes of human PCOS and1mg/kg.dletrozole is better than0.5mg/kg.d one in buliding PCOS rat models.2.Irisin and FNDC5mRNA expression are lower in PCOS groups than innon-PCOS groups. In PCOS groups, Irisin has significantly negative correlations withbody weight, T, LH, INS, HOMA-IR and LEE index，which indicate that Irisin mayplay a certain role in PCOS pathogenesis and it may be a good predictor for theoutcome and treatment of PCOS.