The Expression Of Omentin-1in Polycystic Ovary Syndrome Model Rats And The Interventional Effect Of Metformin

Objective:Polycystic ovary syndrome (PCOS) is a complex andheterogene clinical syndrome which involved in many kinds of factors such asnerve, endocrine and metabolism and ovarian local regulation and so on, andits clinical feature are ovulation disorders, hyperandrogenism andhyperinsulinemia and insulin resistance.Adipose tissue, especially visceraladipose tissue,as one of classical insulin target tissues, plays an importantrole in the occurrence and development of insulin resistance.Also,adiposetissue that is a important endocrine organ can secrete many bioactivesubstances,also known as adipocytokines.As a novel adipokine,Omentin-1participates in glycolipid metabolism, inflammation,vascular functionextensively, especially has a close relationship with metabolic syndrome.In theforeign research showed the low expression of omentin-1in PCOS that is akind of metabolic syndrome disease,but it is still rarely reported in China. Forthe PCOS patients with IR,the insulin-sensitising drug has been applied inclinical practice gradually,and metformin is used most commonly.Therefore,in the study,we established the PCOS rats model by the injection of androgensubcutaneously.The characteristics of the model were similar to humanPCOS.After metformin treatment,we try to observe the expression change ofomentin-1in normal rats and PCOS rats and the intervention effect ofmetformin,so as to further research and discusses the pathogenesis ofpolycystic ovary syndrome and the therapeutic effect of metformin in PCOS.Methods:Forty-five female SD rats(21day) were randomly divided intothree groups:11in normal control group(NC),17in PCOS model group (MO)and17in metformin treatment group (MF)after two days of adaptive feeding.The rats in MO and MF were given1mg/100g weight androgensubcutaneously once a day for five weeks, while rats in NC were given saline in the same volume simultaneously. At five weeks after injection,the rats inMO and MF whose serum testosterone rise and cervical mucus smear appearsheep dentate crystallization continuously conform to PCOS model. And thenthe rats in MF were intragastrically perfused with metformin200mg/kgdissolved in sterilized distilled water every day for three weeks, while rats inNC and MO were given sterilized distilled water in the same volumesimultaneously.At last,In all chloral hydrate anaesthetized rats,sample of bloodwer eobtained to measure fasting blood glucose (FBG), thenradioimmunoassay was used to measure the levels of the serum testosterone(T), estradiol (E2) and progesterone (P), luteinizing hormone (LH),follicle-stimulating hormone (FSH), fasting insulin (FINS) and enzyme linkedimmune method was used to measure the levels of the serumomentin-1,tumour necrosis factor-alpha.The bilateral ovarian tissue wereweighed and prepared for staining with hematoxylin and eosin to observe thechange of ovarian morphology. All the data were dealt with SPSS13.0.Results:1The rats’ body weights were no difference before the experiment, aftereight weeks, the body weights were still no difference between MO and NC (P>0.05), but there were decrease in MO were higher than NC and MO (P <0.05).The ovary weight, ovary weight/body weight in MO and MF werehigher than NC (P <0.05, P <0.05,P <0.05, P <0.05),but there weredecrease in MF than MO (P <0.05).2After5weeks,in MO and MF, except5rats,the rats lose regular estruscycle and all were sheep dentate crystallization,which indicating there were noovulation.In NC,the rats still keep regular estrus cycle and sheep dentatecrystallization and ellipsoids were visible. After8weeks,the MO rats were notyet restore ovulation, the MF rats partially, while the NC rats still keep regularestrus.3The MO and MF rats’ ovaries looked pale with dilated vesicles andgerminal epithelium were thickened while the NC rats’ ovaries were reddishand looked smooth.Through the microscopy, it was possible to see the early development of little follicles and atretic follicles and cystic dilatation folliclesincreased significantly with oocytes disappear,a thin layer of granulosa cellsand a thick layer of thecal cells.It was also can be seen the decreased numberof corpus luteum. The MF rats also have the change, but a lesser degree thanMO rats. The NC can be seen multiple corpus luteum and differentdevelopment stage of the follicles with a thick layer of complete and orderlygranulosa cells.4Compared with NC,there was significant increase in serum testosteronein MO(P<0.05)after8weeks,and there were decrease in serum estrogen,progestogen in MO(P<0.05,P<0.05)but there were no difference in luteinizinghormone,follicle-stimulating hormone,luteinizing hormone/follicle-stimulating hormone between the two groups(P>0.05，P>0.05,P>0.05).Serumprogestogen in MF was higher than MO(P<0.05).But compared with NC,therewere no difference in serum testosterone, estrogen,luteinizing hormone,follicle-stimulating hormone,luteinizing hormone/follicle-stimulatinghormone in MF (P>0.05,P>0.05,P>0.05，P>0.05,P>0.05).5Compared with NC,there were significant increase in serum fastingblood glucose,fasting insulin and homeostasis model assessment-insulinresistance in MO(P<0.05,P<0.05,P<0.05).Compared with MO,serum fastingblood glucose,fasting insulin and homeostasis model assessment-insulinresistance were markedly decrease in MF(P<0.05,P<0.05,P<0.05).6Compared with NC,there was significant increase in serum tumournecrosis factor-alpha in MO(P<0.05).Compared with MO,serum tumournecrosis factor-alpha was markedly decrease in MF(P<0.05).7Compared with NC,there was significant decrease in serum omentin-1in MO(42.83±30.34,P<0.05).Compared with MO,serum omentin-1wasmarkedly increase in MF(70.01±32.39,P<0.05).8Related analysis showed that omentin-1had positive correlation withprogestogen (P<0.05),and omentin-1had negative correlation with ovaryweight/body weight,testosterone, fasting insulin,homeostasis modelassessment-insulin resistance,tumour necrosis factor-alpha(P<0.05,P<0.05， P<0.05,P<0.05,P<0.05),but omentin-1was no obvious correlation withestrogen,luteinizing hormone/follicle-stimulating hormone,fasting bloodglucose(P>0.05,P>0.05,P>0.05).Conclusions:1Rat model of Polycystic ovary syndrome could be established byinjecting androgen,and the model characterized by ovulation and metabolicdisorders features analog to human.So this model could be used to study thepathogenesis of polycystic ovary syndrome and the direct effect ofintervention factors on polycystic ovary syndrome.2The serum omentin-1was decreased markedly and the TNF-α wasincreased markedly in PCOS model group,it showed that the expressionchange of omentin-1and TNF-αwas closely related to the pathogenesis ofPCOS and may play an important role in PCOS and omentin-1maybe the oneof diagnosis index in PCOS.3Metformin has a protective effect on PCOS by increasing the serumomentin-1level.