The Effects Of Kidney-invigorating And Sputum-dispersing Formul A On Glucose And Lipid Metabolism For The PCOS Mouse

Objective：To establish and use a polycystic ovarian syndrome (PCOS) murine model tostudy the effects of kidney-invigorating and sputum-dispersing formula on glucoseand lipid metabolism; and to use the estrous cycle, oral glucose tolerance test (OGTT)and relevant parameters to evaluate the mouse reproductive and metabolic phenotype.Through comparison of the treatment and control groups, the mechanisms ofkidney-invigorating and sputum-dispersing formula in the treatment of PCOS will bediscussed.Methods：95female pre-pubertal (21days old) mice of the SD strain were randomlyassigned into PCOS model group and normal control group. The model groupconsisted of70mice injected sub-cutaneously with DHEA (6mg/100g body weight,mixed with0.2ml oil) daily for20consecutive days. The normal control groupconsisted of25mice injected sub-cutaneously with0.2ml oil daily for20consecutivedays.20days later,10mice from the model group, and10from the normal controlgroup were randomly selected for Homeostasis Model Assessment (HOMA).The remaining75model mice were randomly assigned into5groups of15–model control group, normal control group, metformin group, low-dosage herbs group,and high-dosage herbs group. The model control group and the normal control groupwere gavaged with0.5%saline; metformin group with200mg/kg metformin;low-dosage group with16.6g herbs/kg,20ml/kg; and high-dosage group with33.2gherbs/kg,20ml/kg. After treatment for28days, OGTT was assessed and estrouscycles were determined by analysing the cell types in vaginal smears. Thereafter themice were anesthetised with10%cloral hydrate and5ml blood samples were obtainedfrom the abdominal aorta. Sera were separated and kept at-80oC; dissected ovarieswere weighed and fixed in4%(w/v) paraformaldehyde.Results：Model evaluation 1. Model mice were persistently estrous, with the observation of cornified cells.Normal control mice showed regular estrous cycles.2. Compared to the normal control group, model mice serum INS was significantlyhigher (P<0.01).3. Compared to the normal control group, the wight of model mice was statisticallyinsignificant(P>0.05). Compared to normal control group, model mice wassignificantly higher intissue (P<0.05).4. Model mice had significantly higher levels of fasting blood glucose (P<0.01).Compared to normal control group, model mice AUC was significantly higher(P<0.05).5. Compared to the normal control group, model mice fasting insulin, HOMA-IR andISI was significantly higher (P<0.01).Treatment evaluation1. Model mice were completely acyclic while normal control group showed regularestrous cycles; ovulation in high-dosage group was less affected than inlow-dosage and metformin group.2. Compared to the model control group, normal control, metformin and high-dosagegroups’ serum INS was significantly lower (P<0.01). Compared to the metformingroup, low-dosage group’s serum INS was higher (P<0.01). Compared to themetformin group, high-dosage group’s serum INS was higher (P<0.05).3. Compared to the model control group, normal control, metformin and low-dosagegroups showed insignificant differences in weight (P>0.05). Compared to modelcontrol and metformin groups, the high-dosage group showed significantdifferences in weight (P<0.01and P<0.05respectively). Compared to the modelcontrol group, normal control, metformin and low-dosage groups showedsignificant differences in tissue(P<0.05). Compared to model control andmetformin groups, the high-dosage group’s tissue was significantly lower(P<0.01)4. Compared to the model control group, normal control, metformin, low-dosage,high-dosage groups’ fasting glucose and AUC was significantly lower (P<0.01);compared to metformin group, low-dosage and high-dosage groups’ fastingglucose and AUC was statistically insignificant (P>0.05).5. Compared to the normal control groups, metformin, low-dosage and high-dosagegroups’ HOMA-IR and ISI were significantly lower (P<0.01). Compared to modelcontrol group, high-dosage group fasting insulin was statistically significant (P<0.05). Compared to the low-dosage and high-dosage groups, metformingroup’s HOMA-IR and ISI was lower (P<0.01).Conclusions：1. The generated murine model exhibits many of the endocrine and metabolicfeatures of human PCOS such as hyperinsulinemia, making it an ideal choice forthe study of PCOS.2. Kidney-invigorating and sputum-dispersing formula can improve lipid metabolismand thus lower lipidemia in obese PCOS patients.3. Kidney-invigorating and sputum-dispersing formula can improve insulinresistance and thus lower insulin level. This suggests that lowering of insulin levelcould be a means to correcting hyperandrogenism and improving maturation ofovarian follicles.