Therapeutic effects of glucose-dependent insulinotropic polypeptide receptor antagonists on polycystic ovary syndrome in mice
Objective To investigate the therapeutic effects of glucose-dependent insulinotropic polypeptide(GIP)receptor antagonists on polycystic ovary syndrome(PCOS)in mice.Methods Thirty female C57BL/6 mice were taken and randomly divided into the control,model and intervention groups,with 10 mice in each.Mice in the model and inter-vention groups were fed with high-fat diet combined with subcutaneous injection of dehydroepiandrosterone(DHEA)to es-tablish the PCOS models,and mice in the control group were fed with standard diet.After modeling,the intervention group was given intraperitoneal injection of GIP receptor antagonist,and the model and control groups were given equal vol-ume of normal saline for 28 d.The body mass of the mice was weighed and recorded weekly.Vaginal smears were taken daily from the 7th day of modeling to detect changes in the estrous cycle.At the end of the pharmacological intervention,blood was taken from the tail vein and FPG was measured using a glucometer;blood was taken from the eyeballs,and FINS was measured by ELISA to calculate the insulin resistance index(HOMA-IR);serum testosterone(T),luteinizing hor-mone(LH),and follicle-stimulating hormone(FSH)were measured by ELISA to calculate LH/FSH;and serum GIP and leptin were measured by ELISA.After the blood was taken,mice were executed,the morphology of ovarian tissues was ob-served by HE staining,and GIP protein expression in ovarian tissues was detected by immunohistochemistry.Results Com-pared with the control group,the model group had increased body mass and disordered estrous cycle;compared with the model group,the intervention group had decreased body mass and partially restored estrous cycle.Compared with the con-trol group,FPG,FINS and HOMA-IR increased in the model group;compared with the model group,FINS and HOMA-IR decreased in the intervention group(P<0.05 or P<0.01).Compared with the control group,serum T,LH and FSH were elevated in the model group(all P<0.05);compared with the model group,serum T,LH and FSH were reduced in the intervention group(all P<0.05);no significant difference was found in the LH/FSH among the three groups(P>0.05).Compared with the control group,serum leptin was elevated in the model group(P<0.05);compared with the model group,serum leptin decreased in the intervention group(P<0.05).Compared with the control group,ovarian index was elevated in the model group(P<0.05),and there were obvious polycystic changes in the ovarian tissues;compared with the model group,ovarian index was reduced in the intervention group(P<0.05),and polycystic changes in the ovari-an tissues were improved.Compared with the control group,serum and ovarian GIP were elevated in the model group;compared with the model group,serum and ovarian GIP were reduced in the intervention group(both P<0.05).Conclusion GIP receptor antagonists reduced body mass,restored the estrous cycle,improved insulin resistance,down-regulated serum testosterone,and restored ovarian polycystic changes to some extent in PCOS mice.
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