小檗碱改善多囊卵巢综合征伴胰岛素抵抗大鼠子宫组织局部胰岛素抵抗的作用机制研究

目的 探讨小檗碱对多囊卵巢综合征(PCOS)伴胰岛素抵抗(IR)大鼠血清甾体激素和糖脂代谢指标的影响及可能作用机制.方法 将60只雌性SD大鼠随机分为空白组、PCOS组、小檗碱组和二甲双胍组,每组15只.PCOS组、小檗碱组和二甲双胍组大鼠采用胰岛素联合人绒毛膜促性腺激素(HCG)建立PCOS伴IR模型.造模成功后,小...

Study on the mechanism of berberine in improving local insulin resistance in uterine tissue of rats with polycystic ovary syndrome and insulin resistance

Objective It is to investigate the effect and possible mechanism of berberine on serum steroid hormones and glucose-lipid metabolism indexes in polycystic ovary syndrome(PCOS)rats with insulin resistance(IR).Methods Sixty female SD rats were randomly divided into blank group,PCOS group,berberine group and metformin group,with 15 rats in each group.The rats in PCOS group,berberine group and metformin group were treated with insulin combined with human chorionic gonadotropin(HCG)to establish models of PCOS with IR.After successful modeling,the berberine group and metformin group were respectively given berberine hydrochloride suspension and metformin solution by gavage,and the blank group and PCOS group were given the same amount of normal saline by gavage,all treated for 31 days.Glucose tolerance test(OGTT)was performed,the levels of serum steroid hormones and glucose-lipid metabolism indexes of the rats in each group were detected,and the insulin resistance index(HOMA-IR)was calculated.Hematoxylin-eosin staining(HE)was used to observe the morphology of rat uterus.The protein expression levels of IRS1,AKT and GSK3βin uterine tissue were detected by Western blot method,and the mRNA expression level of GLUT4 in uterine tissue was detected by real-time quantitative PCR(Real-Time PCR).Results Compared with the blank group,the levels of blood glucose at each time period of OGTT and serum luteinizing hormone(LH),17-hydroxyprogesterone(17-OHP),total testosterone(T),androstenedione(ASD),three acylglycerol(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),fasting insulin(FINS),HOMA-IR,LH/follicle stimulating hormone(FSH)of the rats in PCOS group were significantly increased(all P<0.05),the levels of sex hormone-binding globulin(SHBG)and high-density lipoprotein cholesterol(HDL-C)were significantly decreased(all P<0.05),and the thickness of uterine tissue myometrium,the height of luminal epithelial cells and the size of glandular cavity were significantly increased(all P<0.05);compared with the PCOS group,the levels of blood glucose at each time period of OGTT and serum LH,17-OHP,T,ASD,TG,TC,LDL-C,FINS and HOMA-IR,LH/FSH,uterine tissue myometrial thickness,luminal epithelial cell height,and glandular lumen size of the rats in the berberine group and metformin group were significantly decreased(all P<0.05),and SHBG levels were significantly increased(all P<0.05).Compared with the blank group,the relative expressions of pIRS1-Ser307 and GSK3βproteins in the uterine tissue of the PCOS group were significantly increased(all P<0.05),and the relative expressions of pAKT-S473 protein and GLUT4 mRNA were significantly decreased(all P<0.05);compared with the PCOS group,the relative expressions of pIRS1-Ser307 and GSK3βproteins in the uterine tissue of the rats in the berberine group and metformin group were significantly decreased(all P<0.05),and the relative expressions of pAKT-S473 protein and GLUT4 mRNA were significantly increased(all P<0.05).Conclusion Berberine can improve the hyperinsulinemia,reproductive endocrine and glucose and lipid metabolism disorders in rats with PCOS and IR,which may improve the local IR of the uterus by regulating the expressions of IRS1,AKT,GSK3βprotein and GLUT4 mRNA in the uterine insulin signaling pathway,thus to improve endometrial receptivity and uterine dysplasia status.