茯苓酸改善多囊卵巢综合征大鼠胰岛素抵抗的作用及机制研究OACSTPCD

OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome(PCOS)and its mechanism.METHODS One hundred and twenty-six female rats were randomly separated into blank group,PCOS group,poria acid low-dose group(8.33 mg/kg),pachymic acid high-dose group(33.32 mg/kg),ethinylestradiol cyproterone group(positive control group,0.34 mg/kg),recombinant rat high mobility group protein B1 protein(rHMGB1)group(8 μg/kg),and poria acid high dose+rHMGB1 group(33.32 mg/kg poria acid+8 μg/kg rHMGB1),with 18 rats in each group.Except for the blank group,the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model.After successful modeling,administration was performed once a day for 4 weeks.After medication,the fasting blood glucose and fasting insulin levels,and insulin resistance index(HOMA-IR)were measured in rats;the levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH)and testosterone(T)in rat serum,and the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in ovarian tissue were detected;ovarian coefficients of rats were calculated;the pathological changes of ovarian tissue were observed;the expressions of HMGB1,receptor for advanced glycosylation end product(RAGE)and phosphorylated nuclear factor κB p65(p-NF-κB p65)proteins were determined in ovarian tissue of rats.RESULTS Compared with the blank group,the pathological injury of ovarian tissue of rats in the PCOS group was serious,the levels of fasting blood glucose and fasting insulin,HOMA-IR and ovarian coefficient were increased,the levels of serum LH and T were increased,while the levels of FSH were decreased;the levels of IL-1β and TNF-α,the expressions of HMGB1,RAGE and p-NF-κB p65 protein in ovarian tissue were increased,with statistical significance(P＜0.05).Compared with the PCOS group,pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group,and fasting blood glucose,fasting insulin levels,HOMA-IR and ovarian coefficient were decreased;serum LH and T levels were decreased,while FSH levels were increased;the levels of IL-1β and TNF-α and the expressions of HMGB1,RAGE and p-NF-κB p65 protein in ovarian tissue were decreased,with statistical significance(P＜0.05).The trend of corresponding indexes in rHMGB1 group was opposite to the above(P＜0.05).Compared with poria acid high-dose group,the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group(P＜0.05).CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/RAGE pathway.