Objective:To explore the effect of curcuminon the insulin receptor substrate1(IRS1)/phosphatidylinositol-3-kinase(PI3K)/endometrial expression of glucose 4(GLUT4)signalling pathway and its regulator,phosphatase and te...Objective:To explore the effect of curcuminon the insulin receptor substrate1(IRS1)/phosphatidylinositol-3-kinase(PI3K)/endometrial expression of glucose 4(GLUT4)signalling pathway and its regulator,phosphatase and tensin homolog(PTEN),in a rat model of polycystic ovarian syndrome(PCOS).Methods:PcoS model was induced by letrozole intragastric administration.Sprague-Dawleyrats were randomized into 4groups according to a random number table:(1)control group;(2)PcoS group,which was subjected to PCOS and received vehicle;(3)curcumin group,which was subjected to PCoS and treated with curcumin(200 mg/kg for 2 weeks);and(4)curcumin+LY294002 group,which was subjected to PCOS,and treated with curcumin and LY294002(a specific PI3K inhibitor).Serum hormone levels(17β-estradiol,follicle stimulating hormone,luteinizinghormone,progesterone,and testosterone)were measured by enzyme linked immunosorbentassay,and insulin resistance(IR)was assessed using the homeostasismodel assessment of IR.Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination.Expression levels of key transcriptional regulators and downstream targets,including IRS1,Pl3K,protein kinase B(AKT),GLUT4,and PTEN,were measured via reverse transcription polymerase chain reaction and Western blot,respectively.Results:The Pcos group showed impaired ovarian morphology and function.Compared with the PCoS group,curcumin treatment exerted ovarioprotective effects,down-regulated serum testosterone,restored IR,inhibited inflammatory cell infiltration in ovarian tissues,decreased IRS1,PI3K,and AKT expressions,and up-regulated GLUT4 and PTEN expressions in PCOS rats(P<0.05orP<0.01).In contrast,IRS1,PI3K,AKT,and PTEN expression levelswerenot significantly different between PCOS and curcumin+LY294002 groups(P>0.05).Conclusion:The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions,in which,PTEN,a new target,may play a role in regulating the IRS1/PI3K/GLUT4 pathway.展开更多
基金Supported by the Joint Funds for Innovation of Science and Technology of Fujian Province(No.2018Y9046)the Qihang Foundation Project of Fujian Medical University of China(No.2018QH1023)。
文摘Objective:To explore the effect of curcuminon the insulin receptor substrate1(IRS1)/phosphatidylinositol-3-kinase(PI3K)/endometrial expression of glucose 4(GLUT4)signalling pathway and its regulator,phosphatase and tensin homolog(PTEN),in a rat model of polycystic ovarian syndrome(PCOS).Methods:PcoS model was induced by letrozole intragastric administration.Sprague-Dawleyrats were randomized into 4groups according to a random number table:(1)control group;(2)PcoS group,which was subjected to PCOS and received vehicle;(3)curcumin group,which was subjected to PCoS and treated with curcumin(200 mg/kg for 2 weeks);and(4)curcumin+LY294002 group,which was subjected to PCOS,and treated with curcumin and LY294002(a specific PI3K inhibitor).Serum hormone levels(17β-estradiol,follicle stimulating hormone,luteinizinghormone,progesterone,and testosterone)were measured by enzyme linked immunosorbentassay,and insulin resistance(IR)was assessed using the homeostasismodel assessment of IR.Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination.Expression levels of key transcriptional regulators and downstream targets,including IRS1,Pl3K,protein kinase B(AKT),GLUT4,and PTEN,were measured via reverse transcription polymerase chain reaction and Western blot,respectively.Results:The Pcos group showed impaired ovarian morphology and function.Compared with the PCoS group,curcumin treatment exerted ovarioprotective effects,down-regulated serum testosterone,restored IR,inhibited inflammatory cell infiltration in ovarian tissues,decreased IRS1,PI3K,and AKT expressions,and up-regulated GLUT4 and PTEN expressions in PCOS rats(P<0.05orP<0.01).In contrast,IRS1,PI3K,AKT,and PTEN expression levelswerenot significantly different between PCOS and curcumin+LY294002 groups(P>0.05).Conclusion:The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions,in which,PTEN,a new target,may play a role in regulating the IRS1/PI3K/GLUT4 pathway.
