Xin yixue (Mar 2023)
The effect and mechanism of rapamycin on the ovarian tissue of rats with PCOS induced by dehydroepiandrosterone
Abstract
Objective To evaluate the effect and unravel the mechanism of rapamycin on the ovarian tissues in rat models with polycystic ovary syndrome （PCOS） induced by dehydroepiandrosterone （DHEA）. Methods After 1-week accustomed feeding， 55 rats were randomly divided into the blank （n=13）， control （n=13） and model groups （n=29）. PCOS rat models were established by subcutaneous injection of DHEA solution. In the control group， rats were subcutaneously injected with soybean oil， while those in the blank group were not treated throughout the whole experiment. After the model was successfully established， all rats were divided into the blank group， control group （intraperitoneal injection of an equivalent volume of normal saline）， the model group， low-dose group （intraperitoneal injection of 1 mg/kg rapamycin） and high-dose group （intraperitoneal injection of 10 mg/kg rapamycin） for 28 d，8 rats in each group. Blood glucose and hormone levels were detected， and HE， Masson and immunohistochemical staining was performed after corresponding interventions. The changes of the expression levels of mTOR， p-mTOR and p-P70S6 were assessed among different groups. TUNEL assay was used to detect the apoptosis of ovarian tissues among different groups. Results PCOS rats showed irregular estrous cycle， and the follicles were manifested with polycystic changes. The body weight， ovarian weight， volume， relative weight， sex hormone levels and positive area of ovarian fibrosis of PCOS rats were all higher than those in the control group （all P < 0.05）， whereas these parameters in the low- and high-dose groups were lower than those in the model control group （all P < 0.05）， and the polycystic changes of ovarian tissues were significantly mitigated. The positive area of ovarian fibrosis in the low- and high-dose groups was increased than those in the blank and control groups （all P < 0.05）. The positive area of ovarian fibrosis in the high-dose group was increased than that in the control group （P < 0.05）. No significant difference was noted in the OD value of mTOR protein among five groups （all P > 0.05）. The OD value of mTOR protein in the model control group was higher compared with those in the remaining four groups （all P < 0.05）. The OD value of mp-P70S6 protein in the model control group was similar to that in the control group （P > 0.05）， whereas the OD value of mp-P70S6 protein in the high-dose group was lower compared with those in the blank， control and low-dose groups （all P < 0.05）. TUNEL staining revealed that the apoptosis rate of ovarian tissues in the model control group was higher than those in the blank， control and high-dose groups （all P < 0.005）， whereas the apoptosis rate in the blank group was lower than that in the low-dose group （P < 0.005）. Conclusions Rapamycin can reduce body weight， decrease ovarian mass and volume， lower hormone levels， mitigate polycystic changes in follicular tissues and alleviate apoptosis of ovarian tissues in DHEA-induced PCOS rat models， which may be related to the inhibition of abnormal activation of mTOR signaling pathway by rapamycin. However， rapamycin may aggravate ovarian interstitial fibrosis in PCOS rats. The body weight， ovarian mass and volume of PCOS rats are lower than the normal levels.
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