Effects of erianin on the apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome and its mechanism / 中国药房

ABSTRACT

OBJECTIVE To investigate the effects of erianin （ERI） on the apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome （PCOS） and its mechanism. METHODS PCOS rat model was constructed by subcutaneous injection of dehydroepiandrosterone， and the successfully constructed rats were randomly divided into PCOS group， ERI low-dose， medium- dose and high-dose groups （10， 20， 40 mg/kg） and ERI high dose + verteporfin group （40 mg/kg ERI + 10 mg/kg verteporfin）， with 10 rats in each group. Another 10 normal rats were selected as the normal group. Rats in each administration group were given corresponding dose of ERI and/or intraperitoneal injection of vitiporfin， and rats in the PCOS group and normal group were orally administered an equal volume of 1% dimethyl sulfoxide， once a day， for 6 consecutive weeks. After administration， the body weight， fasting blood glucose （FPG）， serum levels of estradiol （E2）， testosterone （T）， follicle stimulating hormone （FSH） and luteinizing hormone （LH） were detected in each group； morphological changes in ovarian tissue were observed， and the apoptosis of ovarian tissue cells was analyzed. Apoptosis-associated proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3] and Hippo-YAP signaling pathway associated proteins [large tumor suppressor kinase 1 （LATS1）， phosphorylated LATS1 （p-LATS1） and Yes associated protein （YAP）， phosphorylated YAP （p-YAP）， transcriptional co-activator with PDZ binding motif （TAZ）] were detected in ovarian tissue. RESULTS Compared with PCOS group， the ovarian polycystic characteristics of the ERI low-dose， medium-dose，and high-dose groups were reduced， the number of atretic follicles was reduced， and the granulosa cell layer was thickened； the body mass， FPG， T， LH， LH/FSH， the number of cystic follicles， cell apoptosis index， protein expressions of Bax， Caspase-3， p-LATS1 and p-YAP were greatly decreased （P＜0.05）； the number of corpus luteum， protein expressions of E2， Bcl-2， LATS1， YAP and TAZ were greatly increased （P＜0.05）. Compared with ERI high-dose group， the above indexes in ERI high-dose + vitiporfin group were inhibited （P＜0.05）. CONCLUSIONS ERI can promote the proliferation of ovarian granulosa cells and improve the level of sex hormones in PCOS rats， and its mechanism of action may be related to the inhibition of the Hippo-YAP signaling pathway.